Chronic exposure to exogenous matrilysin induces chemoresistance and enhances Bcl-2 expression in A549 lung adenocarcinoma cells.
Matrix metalloproteinase (MMP) family member matrilysin (matrilysin) has been indicated to induce apoptosis-resistance and chemoresistance. The purpose of current study was to investigate the potential capacity of induction cisplatin-resistance upon the unremitting exposure to exogenic matrilysin. At the same time, the expressions of apoptosis-related genes were examined to clarify the underlying mechanisms. A549 lung adenocarcinoma cells was used to establish our chronic exposure models. The viability of A549 lung adenocarcinoma cells was determinated by MTT and the apoptosis was assessed by Hoechst 33342 staining and Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis-relative genes were evaluated by flow cytometry, immunocytochemistry staining and real-time quantitative RT-PCR, respectively. Overall, chronic exposure to crescenting level of exogenous matrilysin (10, 50, 100, 200 ng/ml) did not significantly alter the growth rates of A549 cells. However, a certain range of matrilysin might protect tumor cells from cisplatin-medicated death. The underlying mechanism may due to the Bcl-2 overexpression and imbalance in the ratio of Bcl-2/Bax. Our results offer a potential mechanism to explain the impact of matrilysin on apoptosis and provide new insights into the profound mechanisms of acquired cisplatin-resistance. Further researches are highly suggestive of this association which has great clinical implications.
Liu
Hui
H
Department of Internal Medicine, Division of Pulmonary and Critical Care, The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Street, 510630 Guangzhou, China. huiliu_sums@yahoo.com.cn
Zhang
Tiantuo
T
Wu
Benquan
B
Huang
Jing
J
Zhou
Yuqi
Y
Zhu
Jiaxin
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D020783:Matrix Metalloproteinase 7 / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D020783:Matrix Metalloproteinase 7; D002945:Cisplatin