The anti-tumor effects of the combination of microwave hyperthermia and lobaplatin against breast cancer cells in vitro and in vivo

PI3K/AKT/mTOR通路 癌症研究 蛋白激酶B 细胞凋亡 乳腺癌 活力测定 信号转导 癌症 激酶 转移 细胞生长 自噬 流式细胞术 生物 化学 医学 细胞生物学 免疫学 内科学 生物化学
作者
Xiaohu Li,Xin Zhang,Inam Ullah Khan,Nina Ni Guo,Bing Wang,Yuxin Guo,Bufan Xiao,Yueshan Zhang,Yi‐Min Chu,Jun Song Chen,Fang Guo
出处
期刊:Bioscience Reports [Portland Press]
卷期号:42 (2)
标识
DOI:10.1042/bsr20190878
摘要

Abstract Background: 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. Methods: 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. Result: 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. Conclusion: 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.
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