维生素C增强化疗药顺铂杀伤癌细胞的作用，
并减少使用量，从而 减少对正常细胞的损伤
原文标题：维生素C和顺铂在宫颈癌细胞中通过改变的氧化还原循环和p53的上调诱导细胞死亡
Vitamin C in synergism with cisplatin induces cell death in cervical cancer cells through altered redox cycling and p53 upregulation
《癌症研究与临床肿瘤学杂志》第142期(12)·2016年9月。
研究机构：印度免疫学研究所
目的:宫颈癌是世界上女性第二大最流行的癌症。以顺铂为基础的化疗改善了患者的生存率，但由于其对许多组织(尤其是肾毒性)的不良影响，其疗效有限。
为了优化顺铂（CDDP）的疗效，我们提出了一种联合疗法，使用天然产物，副作用最小。维生素C是一种天然的抗氧化剂，能够在药理浓度下有选择性地靶向癌细胞。维生素C能协同增强化疗药物的活性，而不会增加对正常细胞的毒性。因此，我们利用顺铂和维生素C联合治疗来杀死宫颈癌细胞。
方法:我们阐明CDDP的角色和维生素C对宫颈癌SiHa细胞系的作用，通过使用细胞生长化验,DNA碎片分析,彗星试验,体外形态学评估细胞凋亡(AO / EB和DAPI染色),ROS DCFDA分析,流式细胞仪、生化检测(销售税,谷胱甘肽过氧化氢酶,TPA)和免疫印迹。
结果:我们的研究结果清楚地表明，CDDP和维生素C通过p53的过表达和在SiHa细胞中产生过氧化氢，改善顺铂诱导的细胞死亡和减少诱导死亡的剂量。
结论:这些研究提供了新的方法来对抗宫颈癌的顺铂耐药性。
Article in Journal of Cancer Research and Clinical Oncology 142(12) · September 2016 with
National Institute of Immunology
Purpose: Cervical cancer is the second most prevalent cancer in women worldwide. Survival of patients has been improved by cisplatin-based chemotherapy, but its effectiveness is limited due to its adverse effects on many tissues, especially nephrotoxicity. To optimize the efficacy of CDDP, we propose a combination therapy using natural products with minimal side effects. Vitamin C being a natural antioxidant is capable of selectively targeting cancer cells at pharmacological concentrations. Vitamin C synergistically enhances the activity of chemotherapeutic agents without increasing toxicity to normal cells. Therefore, we exploited co-therapy with cisplatin and vitamin C to kill cervical cancer cells.
Methods: We elucidated the role of CDDP and VC on cervical cancer cell line (SiHa) by using cell growth assays, DNA fragmentation analysis, comet assay, in vitro morphological assessment of apoptosis (AO/EB and DAPI staining), ROS analysis by DCFDA, flow cytometry, biochemical assays (GST, GSH, NO, catalase, TPA) and Western blotting.
Results: Our results clearly demonstrated that CDDP and VC treatment exhibited ameliorative effect on induction of cell death by p53 overexpression and generation of hydrogen peroxide in SiHa cells, thereby reducing the dosage of CDDP required to induce cell death in cancer cells.
Conclusions: These studies provide novel approaches to combat cisplatin resistance in cervical cancer.
https://www.researchgate.net/publication/307979042_Vitamin_C_in_synergism_with_cisplatin_induces_cell_death_in_cervical_cancer_cells_through_altered_redox_cycling_and_p53_upregulation
Cisplatin binds to the MDM2 RING finger domain and inhibits the ubiquitination activity†
Kaiming Cao,a Xin Ding,a Yaping Sheng,a Yu Wanga and Yangzhong Liu ORCID logo *a
a CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, China
Cisplatin can directly bind to the RING finger domain of MDM2, leading to the zinc-release and protein unfolding. Consequently, cisplatin inhibits the MDM2-mediated ubiquitination, which is the molecular basis of p53 activation. This work provides insight into the cisplatin-induced p53-elevation that is involved in cell apoptosis.
Cisplatin binds to the MDM2 RING finger domain and inhibits the ubiquitination activity - Chemical Communications (RSC Publishing)
https://pubs.rsc.org/en/content/articlelanding/2020/cc/d0cc00203h#!divAbstract
Mdm2-mediated ubiquitylation: p53 and beyond | Cell Death ...
https://www.nature.com/articles/cdd200968
Jun 05, 2009 · A key Mdm2 function is to promote ubiquitylation and proteasomal-dependent degradation of the tumor suppressor protein p53. Recent reports provide novel important insights into Mdm2-mediated...
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