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 it’s 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 JNK signaling pathway, suppressed the AKT/mTOR signaling pathway, and downregulated IAP and Bcl-2 family protein expression. Conclusion: These results indicate that lobaplatin is an effective breast cancer antitumor 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. Key words: lobaplatin, microwave hyperthermia, apoptosis, autophagy, mTOR, JNK

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