The Effect of Cisplatin on Cytotoxicity of Anticancer Cytokine TRAIL and Its Receptor-Selective Mutant Variant DR5-B

Gasparian M. E.; Bychkov M. L.; Yagolovich A. V.; Kirpichnikov M. P.; Dolgikh D. A.

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The Effect of Cisplatin on Cytotoxicity of Anticancer Cytokine TRAIL and Its Receptor-Selective Mutant Variant DR5-B

机译：顺铂对抗癌细胞因子TRAIL及其受体选择性突变体DR5-B细胞毒性的影响

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Cytokine TRAIL selectively induces apoptosis in vitro and in vivo in tumor cells without affecting normal cells, but its therapeutic application is limited, since many primary tumors are insensitive to TRAIL. To improve the efficiency of TRAIL, we have previously developed TRAIL mutant variant DR5-B, which binds the apoptosis-inducing death receptor DR5 as efficiently as wild type TRAIL, but shows almost no affinity to other receptors. In this study, we investigated the effect of the chemotherapeutic agent cisplatin on the cytotoxicity of TRAIL variants in 12 tumor cell lines of various origin. Cisplatin effectively enhances the cytotoxic activity of TRAIL preparations. The synergistic effect is most pronounced in the prostate cancer cell lines, where the combined effect exceeds the sum of the separate effects by more than 2 times. The cytotoxicity of DR5-B variant is significantly higher compared to wild-type TRAIL in combination with cisplatin in 9 of 12 tumor cell lines.

机译：细胞因子TRAIL在肿瘤细胞中选择性地诱导体内和体外凋亡而不影响正常细胞，但由于许多原发性肿瘤对TRAIL不敏感，因此其治疗应用受到限制。为了提高TRAIL的效率，我们先前已经开发了TRAIL突变体DR5-B，该突变体与诱导凋亡的死亡受体DR5结合的能力与野生型TRAIL一样高，但几乎不与其他受体亲和。在这项研究中，我们研究了化学治疗剂顺铂对TRAIL变体在12种不同来源的肿瘤细胞系中的细胞毒性的影响。顺铂可有效增强TRAIL制剂的细胞毒活性。协同作用在前列腺癌细胞系中最明显，其中联合作用超过单独作用的总和超过2倍。在12种肿瘤细胞系中的9种中，与野生型TRAIL联合顺铂相比，DR5-B变体的细胞毒性明显更高。

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《Doklady biochemistry & biophysics》 |2017年第novaadeca期|385-388|共4页
作者
Gasparian M. E.; Bychkov M. L.; Yagolovich A. V.; Kirpichnikov M. P.; Dolgikh D. A.;
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Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia;

Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia;

Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia;

Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia;

Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia;

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1. A New Efficient Method for Production of Recombinant Antitumor Cytokine TRAIL and Its Receptor-Selective Variant DR5-B [J] . Yagolovich A. V., Artykov A. A., Dolgikh D. A., Biochemistry . 2019,第6期

机译：一种新型高效生产重组抗肿瘤细胞因子痕迹及其受体选择性变体DR5-B.
2. Generation of new TRAIL mutants DR5-A and DR5-B with improved selectivity to death receptor 5 [J] . Gasparian ME, Chernyak BV, Dolgikh DA, Apoptosis: An international journal on programmed cell death . 2009,第6期

机译：产生新的TRAIL突变体DR5-A和DR5-B，对死亡受体5的选择性提高
3. Generation of new TRAIL mutants DR5-A and DR5-B with improved selectivity to death receptor 5 [J] . Marine E. Gasparian, Boris V. Chernyak, Dmitry A. Dolgikh, Apoptosis . 2009,第6期

机译：产生新的TRAIL突变体DR5-A和DR5-B，对死亡受体5的选择性提高
4. EFFECT OF THE NOVEL CHEMOPROTECTANT DRUG, TAVOCEPT~(TM), ON IN VITRO CYTOTOXICITY OF CISPLATIN AND CISPLATIN/PIROXICAM COMBINATION THERAPY AGAINST CANINE TRANSITIONAL CELL CARCINOMA OF THE BLADDER [C] . Carolyn Henry, Aulma Parker, Min Zhao, Annual Conference of the Veterinary Cancer Society . 2009

机译：新型化学防护药物，Tavopect〜（TM）的影响，对顺铂和顺铂/吡洛昔康组合治疗膀胱犬转型细胞癌的体外细胞毒性
5. Evaluation of the mechanism of enhancement of cisplatin cytotoxicity by O(6)-benzylguanine. [D] . Rabik, Cara Anne. 2008

机译：O（6）-苄基鸟嘌呤增强顺铂细胞毒性机制的评价。
6. Genetically Modified DR5-Specific TRAIL Variant DR5-B Revealed Dual Antitumor and Protumoral Effect in Colon Cancer Xenografts and an Improved Pharmacokinetic Profile [O] . Anne V. Yagolovich, Artem A. Artykov, Tatiana A. Karmakova, 2020

机译：遗传修饰的DR5特异性TRAIL变体DR5-B揭示了结肠癌异种移植物中的双抗肿瘤和标志效应和改进的药代动力学曲线
7. Chemotherapeutic Agents Sensitize Resistant Cancer Cells to the DR5-Specific Variant DR5-B more Efficiently than to TRAIL by Modulating the Surface Expression of Death and Decoy Receptors [O] . Аrtem А. Аrtykov, Dmitry A. Belov, Victoria O. Shipunova, 2020

机译：化学治疗剂通过调节死亡和诱饵受体的表面表达，更有效地敏感抗癌细胞对DR5特异性变体DR5-B的抗性癌细胞

The Effect of Cisplatin on Cytotoxicity of Anticancer Cytokine TRAIL and Its Receptor-Selective Mutant Variant DR5-B

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