Endometrial cancer (EC) is the fourth most common malignancy in women in developed countries. The prognosis of EC is extremely poor, and it is an important factor that contributes to the death of patients. Therefore, studying EC pathogenesis and therapeutic targets, and exploring effective drugs are the primary tasks to improve the prognosis of EC. In the present study, we aimed to explore the function of ginkgolic acid (GA) in EC cell apoptosis and autophagy through PI3K/Akt/mTOR signal pathway in vitro and in vivo. Firstly, MTT assay and clone formation assay were employed to analyze the Ishikawa and HEC-1-B cell viabilities and proliferation after treatment with GA. The results showed that GA inhibited endometrial cancer cell survival. Flow cytometry assay and western blot assay were applied to examine the apoptosis and apoptosis related protein Bcl-2, Bax, Cleaved caspase-3 expression levels of Ishikawa and HEC-1-B cells after treatment with GA. Next, we applied western blot assay to analyze the autophagy associated proteins LC3I, LC3II, p62 and Beclin-1 in GA treated Ishikawa and HEC-1-B cells. We found that GA promoted apoptosis and induced autophagy of endometrial cancer cells. Meanwhile, western blot assay was also used to determine the expression levels of the PI3K/Akt/mTOR signal pathway related protein and the results revealed that GA inhibited the activity of PI3K/Akt/mTOR pathway. Finally, we found that GA inhibited tumor growth in vivo through immunohistochemistry assay. In conclusion, GA induces apoptosis and autophagy of EC cells via inhibiting PI3K/Akt/mTOR pathway in vivo and vitro.

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Purpose: To investigate the role and mechanisms of action of long non-coding RNA (lncRNA) (LINC00461) in breast cancer. Methods: Human breast cancer cell lines and normal mammary epithelial cell lines as well as their corresponding negative controls (NC) were cultured and co-transfected with Lipofectamine 3000. Expressions of LINC00461 and miR-607 were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), while the SLC1A3 level was evaluated by western blot. The role of LINC00461 in cell proliferation, apoptosis, cycle arrest, glycolysis, and chemoresistance was determined by MTT, colony formation, flow cytometry, and ELISA assays. Results: The LINC00461 level was overexpressed in breast cancer cell lines (p ˂ 0.05). Knockdown of LINC00461 in MCF-7 cells inhibited cell viability (p ˂ 0.01) and the degree of colony formation (p ˂ 0.001), induced cell apoptosis (p ˂ 0.001) and cycle arrest (p ˂ 0.01), and suppressed glucose consumption (p ˂ 0.001), lactate production (p ˂ 0.001), LDHA activity (p ˂ 0.05) and cisplatin sensitivity (p ˂ 0.05). Overexpression of LINC00461 in MDA-MB-468 cells resulted in reverse outcomes. LINC00461 positively regulated the expression of SLC1A3 via miR-607 in breast cancer cells. It was mechanistically established that LINC00461 is bound to miR-607 and miR-607 bound to SLC1A3, and this was confirmed by luciferase assay. Conclusion: LINC00461 induces cell proliferation, cycle arrest, glycolysis, and chemoresistance by modulating miR-607/SLC1A3 axis in breast cancer. The results lay the theoretical basis for monitoring and therapy of breast cancer.