1. Department of General Surgery, Affiliated Hospital of Shaoxing University (Shaoxing Municipal Hospital), Shaoxing, Zhejiang Province, China.
2. Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
3. Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province 310014, China
4. Genetron Health (Hangzhou) Medical Laboratory Co. Ltd, Hangzhou 310000, China
*These authors contributed equally to this work.
Background: The incidence and mortality rate of gastric cancer has markedly declined over the past few decades, due to the progress and advances in the development of diagnostic and treatment regimens. However, there is still a large portion of patients who are first diagnosed during the advanced stage of gastric cancer when chemotherapy is needed. Unfortunately, resistance to chemotherapeutic agents is the most frequent occurrence during treatment, which indicates a need for the discovery of novel therapeutic anticancer drugs. Methods: The tumor-suppression effect of eight different cucurbitacins was evaluated in gastric cancer cell lines, and the Cucurbitacin E (CuE) showing the greatest effect was used in further studies to explore the mechanism and potential synergistic effect of Dox both in vitro and in vivo. Results: Compared with other cucurbitacins, CuE showed the greatest antiproliferative activity against the gastric cancer cell lines. Further investigations revealed that CuE suppressed the growth of gastric cancer cell lines through the induction of G2/M arrest and subsequent apoptosis by impairing AKt activation and reducing its expression in gastric cancer cells. Furthermore, our results indicate that CuE can significantly enhance the cytotoxicity of doxorubicin (Dox) both in vitro and in vivo. Conclusion: In summary, we present the first evidence of the efficacy of CuE for the inhibition of gastric cancer growth and the synergistic antitumorigenic effect of CuE and Dox, both in vitro and in vivo.
Keywords: gastric cancer, Cucurbitacin E, doxorubicin, AKt