RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion

Kuang, Ye-Hong; Chen, Xiang; Su, Juan; Wu, Li-Sha; Liao, Li-Qiu; Li, Dai; Chen, Zhe-Sheng; Kanekura, Takuro

doi:10.1016/j.canlet.2008.11.010

« Previous Next »Cancer Letters
Volume 276, Issue 2 , Pages 189-195, 18 April 2009

RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion

Ye-Hong Kuang
- Department of Dermatology, Xiang Ya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan 410008, China
- The State Key Laboratory of Medical Genetics, Institute of Medical Genetics, Central South University, Changsha, Hunan 410008, China
Xiang Chen
- Department of Dermatology, Xiang Ya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan 410008, China
- The State Key Laboratory of Medical Genetics, Institute of Medical Genetics, Central South University, Changsha, Hunan 410008, China
- Corresponding author. Address: Department of Dermatology, Xiang Ya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan 410008, China. Tel.: +86 731 432 7377; fax: +86 731 432 8478.
Juan Su
- Department of Dermatology, Xiang Ya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan 410008, China
- The State Key Laboratory of Medical Genetics, Institute of Medical Genetics, Central South University, Changsha, Hunan 410008, China
Li-Sha Wu
- Department of Dermatology, Xiang Ya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan 410008, China
- The State Key Laboratory of Medical Genetics, Institute of Medical Genetics, Central South University, Changsha, Hunan 410008, China
Li-Qiu Liao
- Department of General Surgery, Xiang Ya Hospital, Central South University, Hunan, China
Dai Li
- Department of Dermatology, Xiang Ya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan 410008, China
Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, St. John’s University, New York, USA
Takuro Kanekura
- Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Received 16 September 2008; received in revised form 30 October 2008; accepted 7 November 2008. published online 22 December 2008.

Abstract

CD147 (basigin, EMMPRIN) is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. It is highly expressed on the surface of malignant tumor cells to promote their invasiveness and chemo-resistance. The present study aimed to reveal the anti-apoptotic effect of CD147 on the multi-drug resistant (MDR) phenotype of human oral squamous carcinoma cells (SCC) and its possible pathways. Data presented herein showed that MDR derivative SCC KB/V cell line expressed significantly higher CD147 and X-linked inhibitor of apoptosis (XIAP) than its sensitive counterpart KB cells by RT-PCR and Western blot analysis. Down-regulation of CD147 by transfection with CD147 siRNA resulted in decreased XIAP expression. Flow cytometric analysis and electron microscopic observation revealed differential cell apoptotic status related to CD147 expression. Additionally, chemo-sensitivity to 5-fluorouracil of KB/V was increased by CD147 silencing as measured by MTT colorimetric assay. These results suggest that inhibition of CD147 and subsequent XIAP depletion may have an anti-tumor effect through enhancing the susceptibility of cancer cells to apoptosis.

Keywords: Multi-drug resistance, Human oral squamous carcinoma cells, CD147, XIAP, Apoptotic pathways