奥沙利铂与吐根碱和棒曲霉素联合使用对结直肠癌的剂量和顺序依赖性协同作用。

Dose and Sequence Dependent Synergism from the Combination of Oxaliplatin with Emetine and Patulin Against Colorectal Cancer.

作者信息

Alam Md Nur, Yu Jun Q, Beale Philip, Huq Fazlul

机构信息

Discipline of Pathology, Sydney Medical School, A26-RC Mills Room 105, University of Sydney, Sydney, NSW, Australia.

Sydney Cancer Centre, Concord Hospital, Sydney, NSW 2139, Australia.

出版信息

Anticancer Agents Med Chem. 2020;20(2):264-273. doi: 10.2174/1871520619666191021112042.

DOI:10.2174/1871520619666191021112042

PMID:31736447

Abstract

BACKGROUND

Colorectal cancer is the third most commonly diagnosed cancer in the world, causing many deaths every year. Combined chemotherapy has opened a new horizon in treating colorectal cancer. The objective of the present study is to investigate the activity of oxaliplatin in combination with emetine and patulin against colorectal cancer models.

METHODS

IC50 values of oxaliplatin, emetine and patulin were determined against human colorectal cancer cell lines (HT-29 and Caco-2) using MTT reduction assay. Synergistic, antagonistic and additive effects from the selected binary combinations were determined as a factor of sequence of administration and added concentrations. Proteomics was carried out to identify the proteins which were accountable for combined drug action applying to the selected drug combination.

RESULTS

Oxaliplatin in combination with patulin produced synergism against human colorectal cancer models depending on dose and sequence of drug administration. Bolus administration of oxaliplatin with patulin proved to be the best in terms of synergistic outcome. Altered expressions of nine proteins (ACTG, PROF1, PPIA, PDIA3, COF1, GSTP1, ALDOA, TBA1C and TBB5) were considered for combined drug actions of oxaliplatin with patulin.

CONCLUSION

Bolus administration of oxaliplatin with patulin has the potential to be used in the treatment of colorectal cancer, and would warrant further evaluation using suitable animal model.

摘要

背景

结直肠癌是全球第三大常见诊断癌症，每年导致许多人死亡。联合化疗为结直肠癌的治疗开辟了新视野。本研究的目的是研究奥沙利铂与吐根碱和棒曲霉素联合对结直肠癌模型的活性。

方法

使用MTT还原试验测定奥沙利铂、吐根碱和棒曲霉素对人结直肠癌细胞系（HT-29和Caco-2）的IC50值。根据给药顺序和添加浓度确定所选二元组合的协同、拮抗和相加作用。进行蛋白质组学以鉴定与所选药物组合的联合药物作用相关的蛋白质。

结果

奥沙利铂与棒曲霉素联合对人结直肠癌模型产生协同作用，这取决于药物剂量和给药顺序。就协同效果而言，奥沙利铂与棒曲霉素推注给药被证明是最佳的。考虑了九种蛋白质（ACTG、PROF1、PPIA、PDIA3、COF1、GSTP1、ALDOA、TBA1C和TBB5）的表达变化与奥沙利铂和棒曲霉素联合药物作用的关系。