Knockdown of cathepsin L sensitizes ovarian cancer cells to chemotherapy.
Ovarian cancer is a leading gynecological malignancy associated with high mortality. The development of acquired drug resistance is the primary cause of chemotherapy failure in the treatment of ovarian cancer. To examine the mechanism underlying paclitaxel resistance in ovarian cancer and attempt to reverse it, the present study induced a TAX-resistant ovarian cancer cell line, SKOV3/TAX. Cathepsin L (CTSL) has been found to be overexpressed in ovarian cancer. The aim of the present study was to investigate the possible involvement of CTSL in the development of TAX resistance in ovarian cancer. CTSL expression was knocked down in SKOV3 ovarian cancer cells and their phenotypic changes were analyzed. The effects of silenced CTSL on the resistant cell line were investigated by proliferation and apoptosis analysis compared with control SKOV3 cells. CTSL was more highly expressed in SKOV3/TAX cells compared with SKOV3 cells. Paclitaxel treatment downregulated the expression of CTSL in SKOV-3 but not in the paclitaxel-resistant SKOV3/TAX cells. CTSL small hairpin RNA (shRNA) knockdown significantly potentiated apoptosis induced by paclitaxel compared with SKOV3/TAX cells transfected with control shRNA, suggesting that CTSL contributes to paclitaxel resistance in ovarian cancer cells and that CTSL silencing can enhance paclitaxel-mediated cell apoptosis. Thus, CTSL should be explored as a candidate of therapeutic target for modulating paclitaxel sensitivity in ovarian cancer.
Department of Radiation Oncology, Nangfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
Hongmei
H
Zhang
Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
Luosheng
L
Zhang
Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
Lixia
L
Wei
Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
Xingwang
X
Gao
Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
L I
LI
Tang
Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
Wei
W
Gong
Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
N A
NA
Min
Department of Oncology, The 458th Hospital of the People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China.
L I
LI
Zhang
Department of Radiation Oncology, Nangfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Yawei
Y
Yuan
SKOV3/TAX cells; apoptosis; cathepsin L; chemoresistance; ovarian cancer; paclitaxel; proliferation