Oxaliplatin
(Synonyms: 奥沙利铂) 目录号 : GC17716
A DNA-crosslinking agent
Cas No.:61825-94-3
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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| Cell experiment [1]: | |
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Cell lines |
OSCC cells |
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Preparation Method |
In order to determine the effect of oxaliplatin on cell viability, CAL27 cells and SCC25 cells were treated with different concentrations of oxaliplatin for 12, 24, and 48 hours. |
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Reaction Conditions |
0-300uM Oxaliplatin for 12, 24, and 48 hours |
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Applications |
Oxaliplatin inhibited cell viability, migration, and cloning formation of OSCC cells and induced cell death in vitro. |
| Animal experiment [2]: | |
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Animal models |
BALB/c mice |
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Preparation Method |
Subjects were injected intraperitoneally (once every two days) with oxaliplatin (5 mg/kg in PBS, oxaliplatin group) or same volume of PBS (control group). After 21 days, mice were euthanized, and their xenografts were harvested and weighed. |
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Dosage form |
5 mg/kg oxaliplatin for 21 days |
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Applications |
Oxaliplatin inhibited tumor growth of OSCC and caused upregulation of PARP1 in vivo. |
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References: [1]. Li D, Kou Y, et,al. Oxaliplatin induces the PARP1-mediated parthanatos in oral squamous cell carcinoma by increasing production of ROS. Aging (Albany NY). 2021 Jan 20;13(3):4242-4257. doi: 10.18632/aging.202386. Epub 2021 Jan 20. PMID: 33495407; PMCID: PMC7906208. |
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Oxaliplatin is a cytotoxic chemotherapy drug used to treat cancer. Oxaliplatin works by interfering with the development of DNA in a cell. This helps to treat cancer which is caused by cells rapidly growing and dividing out of control.
Oxaliplatin can induce DNA damage in cancer cells. Besides,oxaliplatin can interfere with the cell cycle, promote apoptosis, and induce autophagy in tumor cells[2,3]. Oxaliplatin inhibited cell viability, migration, and cloning formation of OSCC cells and induced cell death in vitro[1]. Oxaliplatin inhibited the growth of HCCLM3 and Hep3B cells.Downregulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL and upregulation of the pro-apoptotic protein Bax during oxaliplatin-induced apoptosis[6]. Oxaliplatin was found to be active against C32 and G361 cell lines with IC50 values of 49.48 and 9.07 uM (1 h exposure), 9.47 and 1.30 uM (4 h exposure), and 0.98 and 0.14 uM (24 h exposure), respectively. At a 24 h exposure oxaliplatin appears to be significantly more active than cisplatin against the G361 cell line[4]. 85-88% of all platinum from oxaliplatin was bound to plasma proteins within the first 5 h with an average half-life of 1.71 +/- 0.06 h. When oxaliplatin was incubated in whole blood, the erythrocytes took up 37.1 +/- 2.1% of the total platinum in 2 h (maximum uptake) which was not exchangeable into plasma[5].
The in vivo anticancer effect of oxaliplatin was studied using a nude mouse subcutaneously implanted with CAL27 cells. The average volume of tumors was markedly smaller in the oxaliplatin group than in the control group. Therefore, these results indicated that oxaliplatin inhibited the growth of xenograft OSCC cells in vivo, which was accompanied by the upregulated expression of PARP1[1]. Oxaliplatin-treated mice displayed reduced weight gain, mechanical allodynia, and exploratory behavior deficits that were not significantly improved by exercise[7]. When investigated oxaliplatin-induced haematological toxicities and splenomegaly in mice, Blood analysis showed dose dependent decreases in white and red blood cell counts, and significant changes in haematological indices.Spleen weight was significantly increased indicating splenomegaly, and red pulp tissue exhibited substantial dysplasia[8]. Oxaliplatin-treated mice displayed reduced weight gain and behavioral deficits. Mice treated over a shorter course had significantly increased STAT3 phosphorylation in gastrocnemius muscles. Mice receiving extended oxaliplatin treatment demonstrated reduced hindlimb muscle mass with upregulation of myopathy-associated genes Foxo3, MAFbx, and Bnip3[9].
References:
[1]. Li D, Kou Y, et,al. Oxaliplatin induces the PARP1-mediated parthanatos in oral squamous cell carcinoma by increasing production of ROS. Aging (Albany NY). 2021 Jan 20;13(3):4242-4257. doi: 10.18632/aging.202386. Epub 2021 Jan 20. PMID: 33495407; PMCID: PMC7906208.
[2]. Wang X, Li M, et,al. On-Demand Autophagy Cascade Amplification Nanoparticles Precisely Enhanced Oxaliplatin-Induced Cancer Immunotherapy. Adv Mater. 2020 Aug;32(32):e2002160. doi: 10.1002/adma.202002160. Epub 2020 Jun 28. PMID: 32596861.
[3]. Yan S, Zhou N, et,al. PFKFB3 Inhibition Attenuates Oxaliplatin-Induced Autophagy and Enhances Its Cytotoxicity in Colon Cancer Cells. Int J Mol Sci. 2019 Oct 30;20(21):5415. doi: 10.3390/ijms20215415. PMID: 31671668; PMCID: PMC6862230.
[4]. Mohammed MQ, Retsas S. Oxaliplatin is active in vitro against human melanoma cell lines: comparison with cisplatin and carboplatin. Anticancer Drugs. 2000 Nov;11(10):859-63. doi: 10.1097/00001813-200011000-00010. PMID: 11142694.
[5]. Pendyala L, Creaven PJ. In vitro cytotoxicity, protein binding, red blood cell partitioning, and biotransformation of oxaliplatin. Cancer Res. 1993 Dec 15;53(24):5970-6. PMID: 8261411.
[6]. Wang Z, Zhou J, et,al. Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth. Expert Opin Investig Drugs. 2009 Nov;18(11):1595-604. doi: 10.1517/13543780903292626. PMID: 19780708.
[7]. Lees JG, Abdulla M, et,al. Effect of exercise on neuromuscular toxicity in oxaliplatin-treated mice. Muscle Nerve. 2021 Aug;64(2):225-234. doi: 10.1002/mus.27329. Epub 2021 Jun 12. PMID: 34036599.
[8]. Lees JG, White D, et,al. Oxaliplatin-induced haematological toxicity and splenomegaly in mice. PLoS One. 2020 Sep 2;15(9):e0238164. doi: 10.1371/journal.pone.0238164. PMID: 32877416; PMCID: PMC7467301.
[9]. Feather CE, Lees JG, et,al. Oxaliplatin induces muscle loss and muscle-specific molecular changes in Mice. Muscle Nerve. 2018 Apr;57(4):650-658. doi: 10.1002/mus.25966. Epub 2017 Oct 6. PMID: 28881481.
奥沙利铂是一种用于治疗癌症的细胞毒性化疗药物。奥沙利铂通过干扰细胞中 DNA 的发育起作用。这有助于治疗由细胞快速生长和分裂失控引起的癌症。
奥沙利铂可诱导癌细胞中的 DNA 损伤。此外，奥沙利铂可干扰肿瘤细胞的细胞周期，促进细胞凋亡，诱导肿瘤细胞自噬[2,3]。奥沙利铂抑制 OSCC 细胞的细胞活力、迁移和克隆形成，并在体外诱导细胞死亡[1]。奥沙利铂抑制HCCLM3和Hep3B细胞的生长。在奥沙利铂诱导的细胞凋亡过程中，抗凋亡蛋白Bcl-2和Bcl-xL下调，促凋亡蛋白Bax上调[6]。发现奥沙利铂对 C32 和 G361 细胞系具有活性，IC50 值分别为 49.48 和 9.07 uM（暴露 1 小时）、9.47 和 1.30 uM（暴露 4 小时）以及 0.98 和 0.14 uM（暴露 24 小时）。暴露 24 小时后，奥沙利铂对 G361 细胞系[4] 的活性似乎明显高于顺铂。来自奥沙利铂的所有铂的 85-88% 在前 5 小时内与血浆蛋白结合，平均半衰期为 1.71 +/- 0.06 小时。当奥沙利铂在全血中孵育时，红细胞在2小时内占铂总量的37.1.+/- 2.1%（最大摄取量），不能交换入血浆[5]。
使用皮下植入 CAL27 细胞的裸鼠研究了奥沙利铂的体内抗癌作用。奥沙利铂组的平均肿瘤体积明显小于对照组。因此，这些结果表明奥沙利铂在体内抑制了异种移植OSCC细胞的生长，同时伴随着PARP1[1]的表达上调。奥沙利铂治疗的小鼠表现出体重增加减少、机械性异常性疼痛和探索行为缺陷，而运动并未显着改善这些缺陷[7]。当研究奥沙利铂引起的小鼠血液学毒性和脾肿大时，血液分析显示白细胞和红细胞计数呈剂量依赖性下降，血液学指标发生显着变化。脾脏重量显着增加表明脾肿大，红髓组织显着发育不良[8 ].奥沙利铂处理的小鼠显示出体重增加减少和行为缺陷。经过较短疗程治疗的小鼠腓肠肌中的 STAT3 磷酸化显着增加。接受奥沙利铂延长治疗的小鼠表现出后肢肌肉量减少，肌病相关基因 Foxo3、MAFbx 和 Bnip3[9] 上调。
| Cas No. | 61825-94-3 | SDF | |
| 别名 | 奥沙利铂 | ||
| 化学名 | (1R,2R)-cyclohexane-1,2-diamine;oxalate;platinum(2+) | ||
| Canonical SMILES | C1CCC(C(C1)N)N.C(=O)(C(=O)[O-])[O-].[Pt+2] | ||
| 分子式 | C8H14N2O4Pt | 分子量 | 397.29 |
| 溶解度 | ≥ 3.94mg/mL in Water with gentle warming | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5171 mL | 12.5853 mL | 25.1705 mL |
| 5 mM | 0.5034 mL | 2.5171 mL | 5.0341 mL |
| 10 mM | 0.2517 mL | 1.2585 mL | 2.5171 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
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Oxaliplatin: Detection and Management of Hypersensitivity Reactions
Background: Oxaliplatin is used extensively for the treatment of gastrointestinal cancer and other malignancies, with increased frequency of use in recent years. Hypersensitivity reactions (HSRs) can pose a major problem in clinical practice because they can limit the use of oxaliplatin in the care of malignancies in which it has proven efficacy. Nurses play an integral role in the administration of oxaliplatin; therefore, they need to be well educated in the prevention, detection, and management of HSRs. Objectives: This article reviews the symptoms of HSRs associated with oxaliplatin, the specific management of HSRs associated with oxaliplatin, the role of desensitization, and the potential use of skin testing to better identify patients at risk for HSR. Methods: This article reviews the literature related to the diagnosis, prevention, and management of HSRs associated with oxaliplatin and outlines nurses' role. Findings: Oxaliplatin HSRs can occur at any cycle, but patients are at highest risk after they have received six prior infusions of oxaliplatin.
Oxaliplatin-induced peripheral neuropathy: clinical features, mechanisms, prevention and treatment
Oxaliplatin (OXA) is a commonly used platinum-based chemotherapy drug for colorectal cancer. OXA-induced peripheral neurotoxcity (OIPN) is a comprehensive adverse reaction of OXA. OIPN can be divided into acute and chronic types according to clinical features and different mechanisms. The main clinical features of acute OIPN are cold-sensitive sensory symptoms and neuropathic pain in limbs. In addition to the above symptoms, chronic OIPN also produces autonomic nerve dysfunction. The most important mechanism involved in acute OIPN is the alteration of voltage-gated Na + channels, and nuclear DNA damage in chronic OIPN. There are some methods like reducing exposure to cold, calcium and magnesium salts, amifostine could be beneficial in acute OIPN prevention and dose modification, changing in schedule glutathione, duloxetine, selective serotonin reuptake inhibitors, carbonic anhydrase inhibitor in chronic OIPN prevention. Recent updates are provided in this article in relation to the clinical features, potential mechanisms, prevention and treatment of OIPN.
Chemotherapy-induced peripheral neuropathy-part 2: focus on the prevention of oxaliplatin-induced neurotoxicity
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is regarded as one of the most common dose-limiting adverse effects of several chemotherapeutic agents, such as platinum derivatives (oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib. CIPN affects more than 60% of patients receiving anticancer therapy and although it is a nonfatal condition, it significantly worsens patients' quality of life. The number of analgesic drugs used to relieve pain symptoms in CIPN is very limited and their efficacy in CIPN is significantly lower than that observed in other neuropathic pain types. Importantly, there are currently no recommended options for effective prevention of CIPN, and strong evidence for the utility and clinical efficacy of some previously tested preventive therapies is still limited.
Methods: The present article is the second one in the two-part series of review articles focused on CIPN. It summarizes the most recent advances in the field of studies on CIPN caused by oxaliplatin, the third-generation platinum-based antitumor drug used to treat colorectal cancer. Pharmacological properties of oxaliplatin, genetic, molecular and clinical features of oxaliplatin-induced neuropathy are discussed.
Results: Available therapies, as well as results from clinical trials assessing drug candidates for the prevention of oxaliplatin-induced neuropathy are summarized.
Conclusion: Emerging novel chemical structures-potential future preventative pharmacotherapies for CIPN caused by oxaliplatin are reported.
Lnc-RP11-536 K7.3/SOX2/HIF-1α signaling axis regulates oxaliplatin resistance in patient-derived colorectal cancer organoids
Background: Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet.
Methods: Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α.
Results: In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin.
Conclusion: In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.
Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial
Background: Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.
Methods: In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.
Results: 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).
Conclusion: Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.
Trial registration number: NCT03486678.