Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou, Shanghai 200080, China.
Biosci Rep. 2022 Feb 25;42(2). doi: 10.1042/BSR20190878.
Breast cancer is the main lethal disease among females. The combination of lobaplatin and microwave hyperthermia plays a crucial role in several kinds of cancer in the clinic, but its possible mechanism in breast cancer has remained indistinct.
Mouse models were used to detect breast cancer progression. Cell growth was explored with MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphonyl)-2H-tetrazolium) and colony formation assays. Cell migration and invasion were investigated with a transwell assay. Cell apoptosis was probed with flow cytometry. The expression of apoptosis-associated proteins was examined with Western blots.
Combination treatment decreased breast cancer cell viability, colony formation, cell invasion and metastasis. In addition, the treatment-induced breast cancer cell apoptosis and autophagy, activated the c-Jun N-terminal kinase (JNK) signaling pathway, suppressed the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, and down-regulated IAP and Bcl-2 family protein expression.
These results indicate that lobaplatin is an effective breast cancer anti-tumor agent. Microwave hyperthermia was a useful adjunctive treatment. Combination treatment was more efficient than any single therapy. The possible mechanism for this effect was mainly associated with activation of the JNK signaling pathway, inactivation of the AKT/mTOR signaling pathway and down-regulation of the Bcl-2 and IAP families.
乳腺癌是女性主要的致死性疾病。洛铂联合微波热疗在临床上对多种癌症都有显著疗效，但在乳腺癌中的作用机制仍不明确。
采用小鼠模型检测乳腺癌的进展情况。用 MTS（3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基)-2H-四唑）和集落形成实验检测细胞生长情况。用 Transwell 实验检测细胞迁移和侵袭情况。用流式细胞术检测细胞凋亡情况。用 Western blot 检测凋亡相关蛋白的表达。
联合治疗降低了乳腺癌细胞的活力、集落形成、细胞侵袭和转移。此外，该治疗诱导乳腺癌细胞凋亡和自噬，激活 c-Jun N-末端激酶（JNK）信号通路，抑制蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路，并下调 IAP 和 Bcl-2 家族蛋白的表达。
这些结果表明洛铂是一种有效的乳腺癌抗肿瘤药物。微波热疗是一种有用的辅助治疗方法。联合治疗比任何单一疗法都更有效。这种效果的可能机制主要与 JNK 信号通路的激活、AKT/mTOR 信号通路的失活以及 Bcl-2 和 IAP 家族的下调有关。
