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.
Highlights
Breast cancer is the most frequently diagnosed cancer and the main cause of cancer deaths among females worldwide
Our study indicated that the combination therapy of microwave hyperthermia and lobaplatin-induced autophagy and apoptosis in breast cancer cells
We investigated a combination therapy consisting of lobaplatin and microwave hyperthermia in vivo and in vitro
Summary
Breast cancer is the most frequently diagnosed cancer and the main cause of cancer deaths among females worldwide. Lobaplatin is a third-generation platinum (D-19466, 1,2-diamino-methyl-cyclobutane-platinum (II)-lactate) drug [2] It is considered a potential drug for the treatment of multiple solid tumors, with encouraging anti-cancer activity and low organ toxicity [3–5]. Result: Combination treatment decreased breast cancer cell viability, colony formation, cell invasion and metastasis. 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. 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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