Downregulation of MDM2 expression by RNAi inhibits LoVo human colorectal adenocarcinoma cells growth and the treatment of LoVo cells with mdm2siRNA3 enhances the sensitivity to cisplatin.
To investigate the biological effect of mdm2 in human colorectal adenocarcinoma LoVo cells, three mdm2siRNA constructions were recombined and transient transfected into human colorectal adenocarcinoma LoVo cells with low differentiation character in vitro. The results showed that mdm2siRNA3 reduced mRNA level of mdm2 and protein level of mdm2, leading to proliferation inhibition on LoVo cells, and reduced tumor growth in nude mice. It was found that depletion of MDM2 in this pattern promoted apoptosis of LoVo cells and Cisplatin (DDP) treated in the mdm2siRNA3 transfected cell population would result in a substantial decrease by MTT colorimetry. Decreasing the MDM2 protein level in LoVo cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, which indicated that mdm2 gene played a definite role in the development and aggressiveness of human colon carcinoma. It also could be a therapeutic target in colorectal carcinoma. The synergistic activation of RNAi and cell toxicity agents indicated that the combination of chemotherapy and gene therapy will be a promising approach in the future.
Yu
Yan
Y
Department of Internal Medicine, Cancer Hospital of Harbin Medical University, Harbin 150040, People's Republic of China. gyfyuyan@hotmail.com
Sun
Ping
P
Sun
Li-chun
LC
Liu
Guo-yi
GY
Chen
Guo-hua
GH
Shang
Li-hua
LH
Wu
Hong-bo
HB
Hu
Jing
J
Li
Yue
Y
Mao
Yin-ling
YL
Sui
Guang-jie
GJ
Sun
Xi-wen
XW
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015179:Colorectal Neoplasms; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002945:Cisplatin