Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells.
The successful of anti-cancer treatment are often limited by the development of drug resistance. Recent work has highlighted the involvement of non-coding RNAs, microRNAs(miRNAs) in cancer development, and their possible involvement in the evolution of drug resistance has been proposed. In this study, we combine taxol chemotherapy and miR-21 inhibitor treatment via polyamidoamine (PAMAM) dendrimers vector to evaluate the effects of combination therapy on suppression of breast cancer cells. The 50% inhibitory concentration (IC50) values for taxol were significantly decreased to a greater extent in the cells transfected with miR-21 inhibitor compared with cells treated with taxol alone. Taxol treatment also increased the percentage of apoptotic breast cancer cells in miR-21 inhibitor transfected cells compared with control cells. Furthermore, treatment of the miR-21 inhibitor-transfected cells with the anti-cancer drugs taxol resulted in significantly reduced cell viability and invasiveness compared with control cells. These results indicated that the miR-21 plays an important role in the resistance of breast carcinoma cells to chemotherapeutic drugs. Therefore, miR-21 inhibitor gene therapy combined with taxol chemotherapy might represent a promising novel therapeutic approach for the treatment of breast malignancies.
Mei
Mei
M
Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China P.R.
Ren
Yu
Y
Zhou
Xuan
X
Yuan
Xu-bo
XB
Han
Lei
L
Wang
Guang-xiu
GX
Jia
Zhifan
Z
Pu
Pei-yu
PY
Kang
Chun-sheng
CS
Yao
Zhi
Z
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D050091:Dendrimers / Q000494:pharmacology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D000972:Antineoplastic Agents, Phytogenic; D050091:Dendrimers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C104700:PAMAM Starburst; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel