Dihydroartemisinin suppresses bladder cancer cell invasion and migration by regulating KDM3A and p21.

Emerging evidences have shown that Dihydroartemisinin (DHA), used in malaria treatment, possess anti-cancer activity. However, the study of its potential functional roles and the anti-cancer mechanisms in bladder cancer is limited. We performed this study to elucidate the influence of DHA in the biological behavior of bladder cancer cells and tried to explore the molecular mechanism. The results of CCK-8 assay showed that DHA significantly inhibited bladder cancer cell 5637, UMUC3 and T24 proliferation and the inhibitory effect is dose- and time- dependent. Further mechanism study showed that DHA performed its function via down-regulating the expression of histone demethylase KDM3A and inducing p21 expression. Moreover, wound healing and transwell migration/invasion assays revealed that DHA inhibited the ability of migration and metastasis in bladder cancer cell line T24. Finally, flow cytometry and colony formation assays demonstrated that DHA significantly promoted apoptosis of T24 cells and suppressed tumorigenesis as expected. Taken together, our study identifies the anti-cancer capacity of DHA in bladder cancer and explores the underlying mechanism.

Two novel TSC2 mutations in renal epithelioid angiomyolipoma sensitive to everolimus.

People who suffers renal angiomyolipoma (AML) has a low quality of life. It is widely known that genetic factors including TSC2 mutation contribute to certain populations of renal AML-bearing patients. In this study, we are the first to identify novel TSC2 mutations in one Chinese renal epithelioid AML patient: c.2652C>A; c.2688G>A based on sequencing result from biopsy tissue. These two somatic mutations cause a translational stop of TSC2, which leads to mTORC1 activation. Given the fact that activation of mTORC1 ensures cell growth and survival, we applied its inhibitor, FDA-approved everolimus, to this woman. After months of treatment with everolimus, Computer-Tomography (CT) scan results showed that everolimus successfully reduced tumor growth and distal metastasis and achieved partial response (PR) to everolimu according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Further Blood Routine Examination results showed the concentration of red cell mass, hemoglobin, white blood cell (WBC), platelets and hematocrit (HCT) significantly returned to normal levels indicating patients with these two TSC2 mutations could be effectively treated by everolimus.