Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma.
It has been demonstrated that mTOR/p70S6K pathway was abnormally activated in many cancers and rapamycin and its analogs can restrain tumor growth through inhibiting this pathway, but some tumors including esophageal squamous cell carcinoma (ESCC) appear to be insensitive to rapamycin in recent studies. In the present study, we explored the measures to improve the sensitivity of ESCC cells to rapamycin and identified the clinical significance of the expression of phosphorylated p70S6K (p-p70S6K). The results showed that, after downregulating the expression of p70S6K and p-p70S6K by p70S6K siRNA, the inhibitory effects of rapamycin on cell proliferation, cell cycle, and tumor growth were significantly enhanced in vitro and in vivo. Furthermore, p-p70S6K had strong positive expression in ESCC tissues and its expression was closely related to lymph node metastasis and the TNM staging. These results indicated that p-p70S6K may participate in the invasion and metastasis in the development of ESCC and downregulation of the expression of p-p70S6K could improve the sensitivity of cells to rapamycin in ESCC.
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Zhaoming
Z
Lu
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Kezheng
K
Peng
Institute of Medicine, Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan 450052, China.
Ning
N
Wang
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China; New Drug Research and Development Centre of Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Hong-Min
HM
Liu
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China; New Drug Research and Development Centre of Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
Guiqin
0000-0003-1137-5927
G
Hou
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015870:Gene Expression; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D009367:Neoplasm Staging; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D034741:RNA, Small Interfering; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus