No abstract

Notch 1 is a key component of the Notch pathway, which performs a crucial role in clear cell renal cell carcinoma (CCRCC) development. The present study aimed to investigate whether Notch 1 could serve as a potential target for CCRCC treatment. Firstly, an association analysis was performed using 52 CCRCC cases and 30 normal controls. The results indicated that Notch 1 protein expression in renal tissues was closely associated with the incidence of CCRCC. In addition, higher Notch 1 expression in CCRCC tissues was positively associated with higher tumor-node-metastasis stage and Fuhrman grade, in addition to larger tumor size. Subsequently, an in vitro study was conducted to examine the biological functions of Notch 1 in CCRCC 786-O cells through inhibiting the Notch 1 expression with Notch 1-specific small interfering RNA (siRNA). As a result, the inhibition of Notch 1 expression by increasing concentrations of Notch 1-specific siRNA dose-dependently decreased cell proliferation and increased cell apoptosis in 786-O cells. Furthermore, B-cell lymphoma-2 and procaspase-3 expression exhibited a dose-dependent decrease accompanied with a dose-dependent inactivation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in Notch 1 siRNA-treated 786-O cells. These findings demonstrated that Notch 1 was associated with CCRCC carcinogenesis and progression, the underlying mechanism of which was that Notch 1 acted as an activator for cell proliferation and a suppressor for cell apoptosis through the Akt/mTOR signaling-dependent pathway in CCRCC. In conclusion, the present study confirmed that Notch 1 is a valuable target against cell survival and proliferation in CCRCC treatment.

Prostate cancer (PC) is one of the leading threats to health and vitality, and accounts for about 9% of all male cancer-associated mortality. 1 Considering that the survival and growth of PC cells rely on androgen in its early stages, androgen ablation therapy is frequently used to reduce tumour growth; however, it remains relatively inefficient in the treatment of the late-stage disease termed castration-resistant prostate cancer (CRPC). 2,3 Docetaxel is a common chemotherapy for patients with CRPC, but the responsiveness is rather poor. 4 Even worse, many patients develop resistance to docetaxel, 5 which is the leading cause of chemotherapy failure. Therefore, knowing about the factors implicated in docetaxel resistance and its underlying mechanism may help to improve the present situation encountered in PC treatment. The gene associated with retinoid-interferon mortality (GRIM-19) is a member of GRIMs family that involved in cancer progression. 6 Deletion or downregulation of GRIM-19 has been found in various cancers. 7,8 Through inhibiting the STAT3 signalling pathway, GRIM-19 has been proven to sensitize gastric cancer cells to radiation. 9 In addition, the combination of GRIM-19 gene therapy with low-dose chemotherapeutic drug, cisplatin has been considered as a potent strategy for the treatment of human oral squamous cell carcinoma. 10 These findings imply the potential role of GRIM-19 in enhancing the efficacy of cancer radiotherapy and chemotherapy. Previously, it has been reported that GRIM-19 may be closely