Relationship Between JNK-2 In Renal Clear Cell Carcinoma And The Sensibility Of Sorafenib Targeted Therapy

Objective: 1. To study the JNK- 2 expression in renal clear cell carcinoma tissues and the relationship between JNK- 2 expression and clinical pathological features. 2. To confirm the relationship between JNK- 2 expression level and solafinib therapy sensitivity.Methods: 1. We use immunohistochemical method to detect JNK – 2 expression of tumor specimens from patients with advanced renal clear cell carcinoma. 2.We use si RNA technology to silence the expression and pc DNA3.1 recombinant plasmid transfection technology to over-expression the level of JNK-2 in renal cancer cell lines 786-0、Caki-2 cells respectively. Then, we test JNK- 2 expression and cellular sensitivity to the sorafenib before and after transfection.We use MTT to detect cell proliferation and flow cytometry(FCM) to detect cell apoptosis, Western Blot to detect the level of proliferation and apoptosis related proteins.Results: 1. We use Immunohistochemical to detect the expression of JNK- 2 in advancedrenal clear cell carcinoma and adjacent tissues. The result is as follows. Twenty-one of 32 specimens(65.6%) were detected to be expressing JNK- 2. Progression free survival(PFS)was(646±103)d for JNK- 2 positive patients and(502±89)d for JNK- 2 negative patients(P<0.01). Overall survival(OS)time was(866±75)d for JNK- 2 positive patients and(657±62)d for JNK- 2 negative patients(P<0.01). 2. We use targeted drugs Sorafenib to intervene. The results showed that the groups of JNK-2 gene silenced, compared to the control groups, apoptosis rate and cell proliferation inhibition rate are higher, the level of apoptosis protein- Bax expression is increased, the level of antiapoptotic proteins Bcl-x L expressions is reduced, the level of proliferation Ki67 protein expression is reduced; the group of JNK- 2 Over-expressed compared to the control groups, the apoptosis rate and cell proliferation rate are significantly reduced, the level of Bax expression is reduced, that of Bcl- x L and Ki-67 is increased.Conclusion: 1. The expression of JNK-2 in the renal clear cell carcinoma is higher than adjacent tissues, which is negatively related with the clinical TNM stage, pathological grade. 2. The level of JNK-2 expression can obviously affect the sensitivity of the renal cancer cell lines to the therapy of targeted drug- Sorafenib.