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Sources of Funding: none

Introduction

Molecular target therapy is a new approach to cure renal carcinoma. In the process of cell apoptosis, TRAIL binds to the death receptor 4 (DR4) and 5(DR5), forming a death inducing signaling complex (DISC) complex, thus leading to a subsequent apoptosis process. However, drug resistance of TRAIL is a major roadblock for the application of TRAIL-based cancer therapy, and the mechanisms are poorly understood. Reports have shown Ginsenoside compound K (CK) acted as potential anti-tumor drug in many cancer types. In our study, we investigate the influence of CK on renal cancer cell apoptosis induced by TRAIL, and further explore the potential mechanisms.

Methods

Cell viability was measured by MTs, with TRAIL treated alone or combined used of CK. Cell apoptosis was evaluated by PI/Annexin V staining and flow cytometer. Furthermore, we use western blot to measure the target protein changes.

Results

In this study, we treated CK alone or in combination with TRAIL in Caki, A498 and ACHN cell lines. We found combined treatment of CK and TRAIL significantly increased cell apoptosis rate compared with TRAIL treated alone (Figure. 1A, B, C, D). Furthermore, CK induced DR5 (death receptor 5) expression in a time and concentration manner (Figure. 1E, F, G). To our surprise, the CK-enhanced TRAIL-mediated cell apoptosis was abrogated by addition of DR5siRNA or CHOP siRNA, but not DR4 siRNA (Figure. 1H-O). In addition, we found CK markly inhibited XIAP, surviving, Mcl-1 expression, but have no influence on c-IAP1, c-IAP2, Bcl-2 and Bcl-xl levels (Figure. 1P, Q).

Conclusions

Our results indicate that CK inhibits the aiti-tumor proteins and up-regulates DR5 expression through CHOP signaling, thus enhancing TRAIL-mediated renal cancer cell apoptosis.

Funding

none