The overexpression of maspin increases the sensitivity of lung adenocarcinoma drug-resistant cells to docetaxel in vitro and in vivo.

Abstract

BACKGROUND:

In this study, we found that maspin affects the development of drug resistance in lung adenocarcinoma. Therefore, it is important to clarify the role and mechanism of mammary serine protease inhibitor (maspin) in the regulation of adenocarcinoma drug resistance in order to improve individualized clinical treatment protocols and drug resistance interventions.

METHODS:

Immunohistochemical was used to detect maspin expression in tissue chip samples of 75 patients diagnosed with lung adenocarcinoma and treated with a taxus chemotherapy regimen, and the correlation between maspin, clinicopathological factors, and prognosis was analyzed. The expression of maspin in a human lung adenocarcinoma docetaxel-resistant cell line, SPC-A1/DTX, and its parent cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and western blot assay. MTT and flow cytometry were used to detect the effects of knockdown or overexpression of maspin on chemotherapy sensitivity and apoptosis in lung cancer cells. Tumor cells were also analyzed in vivo to determine their tumorigenic ability and susceptibility to docetaxel.

RESULTS:

Maspin is poorly expressed in lung adenocarcinoma tissue chips that have received a taxus chemotherapy regimen, and is also closely related to poor grading, late stage, lymph node metastasis, and poor prognosis. Maspin has a low expression in drug-resistant cells, and the expression level of maspin decreases significantly with increases in docetaxel concentration and over time. In drug-resistant cells, knockdown of maspin can significantly affect the sensitivity of drug-resistant cells to docetaxel. In the chemotherapy-sensitive strain SPC-A1, maspin was mainly located in the cell nucleus, while in the chemotherapy-resistant strain SPC-A1/DTX, maspin was mainly located in the cytoplasm. An in vivo nude mouse xenograft model showed that an overexpression of maspin significantly increased the inhibitory effect of docetaxel on tumor-bearing tissues and the apoptosis rate, and markedly reduced tumor weight, volume, and the Ki-67-positive rate.

CONCLUSIONS:

In vitro and in vivo experiments show that overexpression of maspin can increase the sensitivity of lung cancer drug-resistant cells to chemotherapy drugs, suggesting that the expression level of maspin could be used as a molecular marker to predict lung cancer drug resistance to docetaxel.

• Authors: Qian Sun, Kai Zhang, Huan Li, Weiwei Chen, Leilei Liu, Guichun Huang, Qun Zhang, Jing Wang, Lu Lu, Longbang Chen, Rui Wang
• Journal: Annals of translational medicine (Ann Transl Med) Vol. 8 Issue 22 Pg. 1522 (Nov 2020) ISSN: 2305-5839 [Print] China
• PMID: 33313267 (Publication Type: Journal Article)
• Copyright: 2020 Annals of Translational Medicine. All rights reserved.