Small cell lung cancer (SCLC) is one of the most lethal malignancies with rapid chemoresistance. Numerous studies have been devoted to reversing chemoresistance. However, it is still far from successful with a clear way to reverse the effect of chemoresistance. Based on our previous study, enriched environment (EE) has a clear effect on improving the mental state of mice and can reduce chemotherapy resistance caused by platinum regimens. In this study we investigated the complex links between benign mental stress (EE) and chemosensitivity of SCLC, and use anti-depressants to improve the mental state of mice to observe its impact on chemosensitivity to platinum regimens, and the underlying mechanism was explored.
The mental state of mice was comprehensive evaluation by behavior tests include: elevated plus maze (EPM), open field experiment (OF), forced swimming (FS). Then, the mice were transplanted subcutaneously and treated with cisplatin, carboplatin and oxaliplatin. Tumor growth and the results of behavior test were analyzed. The tumor was analyzed by gene expression profiling and the differential genes were screened. The expression level of differential genes were examed by real-time PCR, and verified by western bolt and immunohistochemistry, respectively. And then we examined the effects of antidepression drugs inducing chemoresistance in NCI-H69 cell, and ABCG2 blocker was used for chemosensitivity verification in vivo and in vitro.
EE significantly increased the time of movement of the in the EPM (35.24 sec V.S. 16.78 sec, P
Antidepressants can partially mimic the chemotherapeutic effect of EE and we confirm that the mechanism is partially achieved by increasing BDNF and reducing the expression of ABCG2.
Clinical trial identification
Legal entity responsible for the study
Henan Cancer Hospital
Research Foundation of Henan Cancer Hospital (nos. 201511004 to Yufeng Wu)
All authors have declared no conflicts of interest.