[Study of sequence-dependent in vitro effects of zoledronic acid and paclitaxel upon human nasopharyngeal carcinoma cell line HNE1].
OBJECTIVE
To explore the in vitro effects of anti-proliferation and apoptosis-inducing with different sequence regimens of zoledronic acid plus paclitaxel in human nasopharyngeal carcinoma cell line HNE1 so as to explore the optimal sequence regimen of these two drugs and related mechanism.


METHODS
The cytotoxic effects of different sequence schemes of zoledronic acid plus paclitaxel on HNE1 cells were detected by methyl-thiazol-tetrazolium (MTT) assay. Annexin V-FITC/PI double staining flow cytometry (FCM) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to measure the effects of zoledronic acid plus paclitaxel upon apoptosis. The expressions of mRNA of Bcl-2, Bax, Caspase3 and Caspase9 gene were detected by real-time quantitative-polymerase chain reaction (PCR) and protein was detected by Western blot.


RESULTS
All experiment groups enhanced the effect of anti-proliferation by MTT assay (P < 0.05); the treatment of zoledronic acid followed by paclitaxel was superior to the other two regimens (P < 0.05). As detected by FCM, the early apoptotic rate of control group was 2.59% ± 0.28% and the experiment groups were 13.89% ± 0.69%, 11.73% ± 0.54%, 23.97% ± 0.68%, 10.45% ± 0.16% and 8.59% ± 0.74% respectively (P < 0.05). TUNEL assay detected the late apoptosis of HNE1 cells and the experiment groups enhanced the effect of apoptosis-inducing (P < 0.05). The treatment of zoledronic acid followed by paclitaxel was superior to the other regimens (P < 0.05). Such an effect was due to the down-regulation of anti-apoptotic protein Bcl-2 and up-regulations of pro-apoptotic proteins Bax, Caspase3 and Caspase9 at the expression levels of mRNA and protein. There was a greater regulation in the group of zoledronic acid followed by paclitaxel.


CONCLUSIONS
Zoledronic acid can enhance the in vitro effects of anti-proliferation and apoptosis-inducing for paclitaxel on HNE1 cell. The treatment of zoledronic acid followed by paclitaxel may be the optimal regimen. Synergistic induction of apoptosis is via the effects of Bcl-2 family and through the mitochondrial pathway.
Department of Medical Oncology, Cancer Hospital, Shantou University Medical College, Shantou 515031, China.
Wan-lan
WL
Huang
Xu-yuan
XY
Li
Hong-biao
HB
Wang
Wen
W
Lin
Wen-zhao
WZ
Lin
Sui-ling
SL
Lin
Ying-cheng
YC
Lin
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D017239:Paclitaxel