Zoledronic acid inhibits human nasopharyngeal carcinoma cell proliferation by activating mitochondrial apoptotic pathway.
We investigated the apoptosis-inducing effect of zoledronic acid in human nasopharyngeal carcinoma cell HNE-1 and explore the potential mechanism. Human nasopharyngeal carcinoma cell HNE-1 was exposed to various concentrations (0-40 μmol/L) of zoledronic acid. Cell proliferation was studied by an MTT assay. Cell apoptosis was analyzed by flow cytometry and TdT-mediated dUTP nick-end labeling (TUNEL) assay. Cell cycle was analyzed by flow cytometry. Gene expressions were investigated by quantitative real-time PCR, and protein expressions were investigated by Western blot. The results showed zoledronic acid decreased cell proliferation not in a time- or dose-dependent fashion. TUNEL assay, together with Annexin V/propidium iodide FACS analysis, confirmed the increase in apoptotic HNE-1 cells treated with zoledronic acid. Cell cycle analysis showed a larger number of treated cells occupied the S-phase. Quantitative RT-PCR and Western blot revealed that the pro-apoptotic genes, Bad, Bax, and Caspase-9, were upregulated in treated HNE-1 cells, whereas the anti-apoptotic gene, Bcl-2, was downregulated in both mRNA and protein levels. In conclusion, zoledronic inhibits human nasopharyngeal carcinoma cell proliferation by inducing apoptosis via the mitochondrial apoptotic pathway.
Department of Internal Medicine, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, 515031, China.
Xu-Yuan
XY
Li
Ying-Cheng
YC
Lin
Wan-Lan
WL
Huang
Wen
W
Lin
Hong-Biao
HB
Wang
Wen-Zhao
WZ
Lin
Sui-Ling
SL
Lin
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000187:drug effects; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid