Downregulation of survivin by RNAi inhibits the growth of esophageal carcinoma cells.
Esophageal squamous cell carcinoma ranks among one of the most frequent cause of cancer death in the world. Understanding of the molecular mechanisms involved in the pathogenesis of esophageal cancer becomes critical to develop more effective treatments. Elevated expression of survivin in esophageal carcinoma has been reported before and suppression of survivin expression leads to many tumor cells growth inhibition. We hypothesized that downregulation of survivin would inhibit the growth of human esophageal cancer cells. RNA interference directed against survivin was introduced into a human esophageal squamous cell carcinoma cell line KYSE510. Stable clones were selected and western blot analysis was performed to detect the protein level of survivin. Tumor cell growth in vitro and in vivo was assessed by trypan blue exclusion and nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometric analysis and TUNEL assay were used to detect apoptosis in cell culture and in nude mice. We found that RNA interference could efficiently and stably suppress survivin expression in KYSE510 cells. Downregulation of survivin resulted in significantly inhibition of tumor growth in vitro and in vivo. The mechanism appears to be increased induction of apoptosis. Our results suggest a potential role for the targeting of survivin in the treatments of esophageal carcinoma.
Wang
Yihua
Y
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Zhu
Hongxia
H
Quan
Lanping
L
Zhou
Cuiqi
C
Bai
Jinfeng
J
Zhang
Guo
G
Zhan
Qimin
Q
Xu
Ningzhi
N
D017209:Apoptosis; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000473:pathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000077022:Survivin; D013997:Time Factors
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin