In this study, the Bcl-2 inhibitor ABT-737 was used in combination with everolimus to enhance its anti-tumor effectiveness in everolimus-resistant RCC cell lines.
Bcl-2 and Bax, and the activity of caspase-3, evaluated in tissue biopsies from patients, were congruent with resistance to apoptosis in ccRCCs with respect to healthy controls, respectively.
CAIX, p53 and Bcl-2 might play important roles in the transformation from renal cell carcinoma to high malignant sarcomatoid differentiation, and these three immunohistochemical markers are adverse prognostic factors for the survival of patients with RCC with sarcomatoid differentiation.
Transient transfection of miR-133b and miR-135a reduced viability and induced apoptosis by inhibition of JAK2 expression and its phosphorylation and activation of caspase 3 and 7 in all three ccRCC cell lines. p-STAT3 and Bcl-2 expression was reduced after miRNA transfection whereas only slight influence on Bcl-2 L11 (BIM) was detected.
This is the first study to demonstrate the anti-RCC effect of EVO via apoptosis in vitro and in vivo, and activation of JNK and PERK to induce Bcl-2 protein phosphorylation, which led to disruption of the MMP.
The analysis of relative protein factors suggested that silencing TREM-2 downregulated the expression levels of Bcl2 and PCNA, and upregulated the expression levels of Bax and caspase-3 in RCC cell lines.
Mechanically, treatment of RCC cells with zerumbone activated caspase-3 and caspase-9, and finally led to cleavage of PARR In addition, downregulation of Gli-1 and Bcl-2, which were closely related to the chemoresistance of RCC, was observed in zerumbone-treated RCC cells.
RCC growth was associated with a significant decrease in the expression of the anti-apoptotic proteins Bcl-2 and Bcl-(XL) and increase in pro-apoptotic Bax, all of which were reversed by PDTC.
The association of the bcl2-938C/A single nucleotide polymorphism with survival in patients with renal cell carcinoma was also analyzed by Kaplan-Meier curves.
Restoration of DLC-1 expression in RCC cells led to Bcl-2 and caspase-3 mediated apoptosis as well as attenuated the ability of the cells to form RCC tumors in athymic nude mice (P<0.05).
Microenvironment effects on promoting upregulation of matrix metalloproteinases in Bcl-2-overexpressing renal cell carcinoma as a response to doxorubicin treatment inducing the production of metastasis.
It is suggested that the reduced expression of Fas and bcl-2 in RCC compared with the expression in normal kidney is a prominent alteration of apoptotic regulatory molecules.
Taken together, these results suggest that Fas-dependent pathways as well as alternative pathways, which can be inhibited by Bcl-2, exist in renal cell carcinoma.
In renal cell carcinoma (RCC), the role of bcl-2 is not well-defined, though its expression is reportedly low in primary tumors and lacks prognostic value.
We also analyzed the relationship between TCF-4 gene splicing isoforms, proliferation (proliferating cell nuclear antigen labeling index), and apoptosis [antiapoptotic factors (Bcl-2 and Bcl-x(L)), proapoptotic factors (Bak and Bax), and caspase-3] in RCC samples.