Silibinin restores paclitaxel sensitivity to paclitaxel-resistant human ovarian carcinoma cells.
BACKGROUND
Drug resistance and tumor metastasis are the main causes of treatment failure and mortality in cancer patients. Silibinin, a naturally occurring flavanone, has been shown to be a potent sensitizer for apoptosis induced by a variety of anticancer drugs. In this study, whether silibinin could overcome chemoresistance and reduce the invasiveness of A2780/taxol cells was investigated.


METHODS
A2780 and A2780/taxol cells were treated with silibinin alone and in combination with paclitaxel. Cell viability was determined by MTT assay while apoptosis and cell cycle progression were assessed by flow cytometric analysis. Matrigel invasion assays assessed the invasive activity. Protein and mRNA levels influenced by the treatment were studied by Western blots and quantitative real-time PCR.


RESULTS
Silibinin enhanced the sensitivity of A2780/taxol cells to paclitaxel, increased paclitaxel-induced apoptosis and G2/M arrest consistent with the down-regulation of survivin and P-glycoproteins. A2780/taxol cells demonstrated a two-fold increase in invasiveness ability compared to A2780 cells, whereas the invasive potential was reduced dramatically by silibinin.


CONCLUSIONS
These results suggest silibinin in combination with paclitaxel may be a beneficial chemotherapeutic strategy, especially in patients with tumors refractory to paclitaxel alone.
Departments of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 250012 Jinan, ROC.
Liguang
L
Zhou
Peishu
P
Liu
Bo
B
Chen
Yu
Y
Wang
Xuping
X
Wang
Maurizio
M
Chiriva Internati
Mitchell S
MS
Wachtel
Eldo E
EE
Frezza
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use*; D012333:RNA, Messenger; D000077385:Silybin; D012838:Silymarin / Q000627:therapeutic use
D012333:RNA, Messenger; D012838:Silymarin; D000077385:Silybin; D017239:Paclitaxel