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BACKGROUND: Ovarian cancer is a malignant tumor of the female reproductive system, and its mortality rate is as high as 70%. Estrogen receptor α (ERα)-positive ovarian cancer accounted for most of all ovarian cancer patients. ERα can promote the growth and proliferation of tumors. METHODS: The combined effect of All-trans retinoic acid (ATRA) and tamoxifen was obtained by the combination screening of tamoxifen and compound library by MTS. In addition, colony formation assay, flow cytometry analysis, immunofluorescence staining, quantitative real-time polymerase chain reaction (PCR), western blot, and tumor xenotransplantation models were used to further evaluate the efficacy of tamoxifen and ATRA in vitro and in vivo for ER-α-positive ovarian cancer. RESULTS: In our study, we found that All-trans retinoic acid (ATRA) can cooperate with tamoxifen to cause cell cycle arrest and apoptosis and inhibit ERα-positive ovarian cancer in vivo and in vitro. Further exploration of the mechanism found that ATRA can Inhibit genes related to the ERα signaling pathway, enhance the sensitivity of ERα-positive ovarian cancer cells to tamoxifen, and ascertain the effectiveness of tamoxifen and ATRA as treatments for ovarian cancer with an ERα-positive status. CONCLUSION: Combination of ATRA and tamoxifen is a new way for the treatment of ERα-positive ovarian cancer.
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Introduction: Due to the difficulty of early diagnosis, nearly 70% of ovarian cancer patients are first diagnosed at an advanced stage. Thus, improving current treatment strategies is of great significance for ovarian cancer patients. Fast-developing poly (ADP-ribose) polymerases inhibitors (PARPis) have been beneficial in the treatment of ovarian cancer at different stages of the disease, but PARPis have serious side effects and can result in drug resistance. Using PARPis in combination with other drug therapies could improve the efficacy of PRAPis.In this study, we identified Disulfiram as a potential therapeutic candidate through drug screening and tested its use in combination with PARPis. Methods: Cytotoxicity tests and colony formation experiments showed that the combination of Disulfiram and PARPis decreased the viability of ovarian cancer cells. Results: The combination of PARPis with Disulfiram also significantly increased the expression of DNA damage index gH2AX and induced more PARP cleavage. In addition, Disulfiram inhibited the expression of genes associated with the DNA damage repair pathway, indicating that Disulfiram functions through the DNA repair pathway. Discussion: Based on these findings, we propose that Disulfiram reinforces PARPis activity in ovarian cancer cells by improving drug sensitivity. The combined use of Disulfiram and PARPis provides a novel treatment strategy for patients with ovarian cancer.
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Cervical cancer is a common tumor of the reproductive system; however, to the best of the authors' knowledge, the regulation and underlying mechanism of p53 apoptosis-stimulating protein 2 (ASPP2) in cervical cancer has yet to be elucidated. Therefore, the present study aimed to explore the role of ASPP2 in cervical cancer. Tumor tissues were collected for the detection of ASPP2 expression. Experiments wherein ASPP2 was overexpressed were designed to upregulate the expression of ASPP2. The levels of autophagy were subsequently assessed by examining LC3B level via immunofluorescence. Cell Counting Kit-8 assay was then performed to estimate the level of cell proliferation. The cell proliferation level was also measured by EdU staining, and TUNEL assay was used to detect the level of apoptosis. The expression levels of ASPP2, Beclin1 and associated proteins were detected using reverse transcription-quantitative PCR and western blotting analyses. ASPP2 was observed to be markedly reduced in patients with cervical cancer and in cervical cancer cell lines. Overexpression of ASPP2 was found to suppress the expression of Beclin1, and autophagy was also inhibited in cervical cancer cells. Overexpression of ASPP2 also inhibited cell proliferation and promoted apoptosis of cervical cancer cells via the inhibition of autophagy. Additionally, overexpression of ASPP2 was shown to enhance the TNF-related apoptosis-inducing ligand-induced apoptosis of cervical cancer cells via inhibiting autophagy. Taken together, the results of the present study have shown that ASPP2 exerted antitumor effect in cervical cancer by inhibiting cell proliferation and promoting apoptosis partly through inhibiting autophagy. These findings may be useful for the provision of potential targets for cervical cancer therapy.