Oncotarget

Research Papers:

Disruption of the association between drug transporter and actin cytoskeleton abolishes drug resistance in hypertrophic scar

Linlin Su, Lanqing Fu, Yan Li, Fangfang Yang, Min Zhang and Dahai Hu _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:2617-2627. https://doi.org/10.18632/oncotarget.13734

Metrics: PDF 1499 views  |   HTML 2228 views  |   ?  


Abstract

Linlin Su1,*, Lanqing Fu2,*, Yan Li1,*, Fangfang Yang1, Min Zhang1, Dahai Hu1

1Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China

2Department of Orthopedics, Jingzhou Central Hospital, Tongji Medical College of Huazhong University of Science and Technology, Jingzhou, Hubei 434020, China

*These authors contributed equally to this work

Correspondence to:

Linlin Su, email: [email protected]

Dahai Hu, email: [email protected]

Keywords: hypertrophic scar, fibroblasts, P-glycoprotein

Received: September 01, 2016     Accepted: November 22, 2016     Published: December 01, 2016

ABSTRACT

Hypertrophic scar is characterized by the overgrowth of fibroblasts and often considered as a kind of benign skin tumor, thus chemotherapeutic drugs have been used to treat scars. In view of the similarity, this study aims to investigate whether drug resistance in cancer that contributes to the failure of chemotherapy also exists in hypertrophic scar, and what is the possible mechanism. Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts. When scar fibroblasts were pre-treated with PSC833 or probenecid, a P-glycoprotein or MRP1 inhibitor respectively, the resistance to verapamil or etoposide was strongly attenuated. Moreover, co-immunoprecipitation revealed more association of P-glycoprotein/MRP1 with actin filaments in scar fibroblasts than normal fibroblasts. The resistance in scar fibroblasts to verapamil and etoposide was almost abolished when pre-treated with latrunculin-A or a specific anti-actin antibody. Taken together, this study suggests that the enhanced expression of drug resistance-related transporters and their increased association with actin cytoskeleton contribute to the resistance to chemotherapeutic drugs in hypertrophic scar. Thus, down-regulating the expession of drug transporters or disrupting drug transporter-actin filament interaction might be novel and effective ways for hypertrophic scar treatment.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 13734