A commonly used anti-depression first-line prescription drug, sertraline, can effectively inhibit the DNA repair of tumor cells and promote the apoptosis of tumor cells in a low concentration state, so that it is expected to make sertraline "new drug" and become a new type of tumor. Chemotherapy sensitizer. The project, completed by Professor Zhou Chunshui from the Medical Genetics Laboratory of the School of Basic Medicine of Harbin Medical University, was published online at 2 am on August 29, 2017 in the authoritative journal Oncology, a subsidiary of the British Natural Publishing Group. . Translational control tumor protein (TCTP) is a small molecular protein with unique structure. It is often overexpressed in various cancer tissues such as breast cancer, lung cancer, liver cancer and intestinal cancer. It regulates inflammation, anti-apoptosis, and participates in stress response. Regulate cell proliferation and differentiation, tumor reversal and other functions. In recent years, TCTP has become a new important drug target in tumor targeted therapy. In order to further reveal the molecular mechanism of TCTP in tumor cells, Prof. Zhou Chunshui collaborated with Prof. Steven Dijiji, Department of Cell Biology, Harvard Medical School, using avid proteomics technology to systematically screen potential cells in tumor cells. TCTP interacts with protein groups to reveal their functional mysteries. The study found that translational control of tumor protein (TCTP) interacts with a variety of functional proteins involved in DNA damage repair, particularly functional proteins involved in homologous recombination repair. Knocking down the TCTP protein in tumor cells can lead to impaired cell homologous recombination repair, and at the same time enhance the sensitivity of cells to radiation (such as gamma rays) and DNA damage anticancer drugs (such as etoposide). Among the TCTP small molecule chemical inhibitors reported abroad, Zhou Chunshui's research group selected the commonly used antidepressant drug sertraline at home and abroad. After treatment of TCTP-expressing breast cancer cells with low concentration of sertraline, the abundance of TCTP protein in treated cells was significantly reduced, and the sensitivity of treated cells to DNA damage was enhanced. After irradiation with radiation or DNA damage, apoptotic cells were treated. The ratio was significantly increased, suggesting that low concentration sertraline has radiosensitizing and sensitizing effects. Professor Zhou Chunshui's research team found that low concentration of sertraline does not affect cell growth, but also provides a "positive energy" that is significantly sensitized, showing a good anti-tumor practical value. From the perspective of mechanism of action, sertraline may have a better sensitizing effect on tumor patient populations with high levels of TCTP expression. However, Professor Zhou Chunshui also emphasized that the current research conclusions are based on in vitro cell experiments, and the drug metabolism and drug effects in tumor tissues are much more complicated than in vitro. The efficacy of sertraline in strengthening tumors is still needed. Further clinical experimental treatment is validated and optimized. The co-member of the project, the director of the Gamma Knife Treatment Center of the Second Affiliated Hospital of Harbin Medical University, and the director of the radiotherapy expert Zhang Jinwei pointed out that the biggest highlight of this study was the discovery that sertraline can reduce the level of TCTP protein in cells and inhibit DNA repair ability. Improve the sensitivity of tumor radiotherapy and chemotherapy. Because sertraline is a commonly used first-line prescription drug, doctors and cancer patients can try to apply at any time without complicated and long pre-clinical testing. Another member of the research team, Liu Baogang, chief physician of cancer chemotherapy at Harbin Medical University Cancer Hospital, said that many studies have confirmed in the past that at higher concentrations, sertraline itself can inhibit tumor cell proliferation and cause cell death. However, its selectivity is poor, toxicity and side effects are heavy, and its practical value is low. However, in the existing conventional antidepressant doses, sertraline has mild side effects, can not only exert the function of cell sensitization, but also relieve the depression and anxiety of cancer patients. It is a safe and effective drug with two arrows and two arrows. In this regard, Professor Zhou Chunshui and clinical experts suggested that before radiotherapy or before the implementation of DNA damage anticancer drug chemotherapy, doctors and patients can try to use a reasonable dose and course of sertraline, and then apply radiotherapy or drug chemotherapy. Some patients may have unexpected clinical effects. Source: Technology Daily
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Antidepressant sertraline is expected to become a tumor chemotherapeutic sensitizer