Overexpression of LIMK1 promotes migration ability of multidrug-resistant osteosarcoma cells.
Multidrug resistance (MDR) to chemotherapy is a major obstacle in the treatment of cancer and the resistance process is multifactorial. Studies on multidrug resistance mechanisms relied on the availability of cancer multidrug resistance cell lines that have been established. In this study we successfully established a multidrug resistance cell line MG63/VCR derived from human osteosarcoma cell line MG63 based on the induction by vincristine. MG63/VCR cells exhibited high resistance to vincristine and other anticancer drugs, accompanied by upregulated expression of MDR-associated genes MDR1, MRP1, and Bcl-2. Notably, we found that MG63/VCR cells exhibited higher migration ability compared to parental MG63 cells. Moreover, we demonstrated that LIMK1, a key regulator of actin cytoskeleton, was overexpressed at both mRNA and protein levels in MG63/VCR cells and the higher LIMK1 protein level was correlated with higher level of phosphorylated cofilin. In addition, knockdown of LIMK1 abolished the higher migration ability of MG63/ VCR cells. These results suggest that LIMK1 overexpression contributes to the invasion and metastasis of drug-resistant osteosarcoma and reveal LIMK as a novel therapeutic target for drug resistant osteosarcoma.
Department of Orthopedics, China-Japan Union Hospital, Jilin University, Changchun, China.
Hanyang
H
Zhang
Yan
Y
Wang
Fengjuan
F
Xing
Jincheng
J
Wang
Yang
Y
Wang
Hong
H
Wang
Yudan
Y
Yang
Zhongli
Z
Gao
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004317:Doxorubicin / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D054461:Lim Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034741:RNA, Small Interfering; D014750:Vincristine; D004317:Doxorubicin; C515892:LIMK1 protein, human; D054461:Lim Kinases