Inhibition of the Hedgehog Signaling Pathway Depresses the Cigarette Smoke-Induced Malignant Transformation of 16HBE Cells on a Microfluidic Chip

被引:4
|
作者
Qin, Yong-Xin [1 ,2 ]
Yang, Zhi-Hui [3 ]
Du, Xiao-Hui [3 ]
Zhao, Hui [1 ]
Guo, Zhe [1 ]
Wang, Qi [1 ]
机构
[1] Dalian Med Univ, Affiliated Hosp 2, Dept Resp Med, Dalian 116027, Liaoning, Peoples R China
[2] Dalian Med Univ, Affiliated Hosp 1, Dept Crit Care Med, Dalian 116021, Liaoning, Peoples R China
[3] Dalian Med Univ, Affiliated Hosp 2, Dept Sci Res Ctr, Dalian 116027, Liaoning, Peoples R China
关键词
Hedgehog Signaling System; Lung Cancer; Malignant Transformation; Microfluidic Chip; LUNG-CANCER PATIENTS; IN-VITRO; RESISTANCE; GROWTH; MODEL; TUMORIGENESIS; INFLAMMATION; MECHANISMS; RISK;
D O I
10.4103/0366-6999.231525
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The hedgehog signaling system (HHS) plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases. However, little is known about the involvement of HHS in the malignant transformation of cells. This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial (16HBE) cells. Methods: In this study, two microfluidic chips were designed to investigate cigarette smoke extract (CSE)-induced malignant transformation of cells. Chip A contained a concentration gradient generator, while chip B had four cell chambers with a central channel. The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation. The 16HBE cells in chip B were cultured with 12.25% CSE (Group A), 12.25% CSE + 5 mu mol/L cyclopamine (Group B), or normal complete medium as control for 8 months (Group C), to establish the in vitro lung inflammatory-cancer transformation model. The transformed cells were inoculated into 20 nude mice as cells alone (Group 1) or cells with cyclopamine (Group 2) for tumorigenesis testing. Expression of HHS proteins was detected by Western blot. Data were expressed as mean J standard deviation. The t-test was used for paired samples, and the difference among groups was analyzed using a one-way analysis of variance. Results: The optimal concentration of CSE was 12.25%. Expression of HHS proteins increased during the process of malignant transformation (Group B vs. Group A, F = 7.65, P < 0.05). After CSE exposure for 8 months, there were significant changes in cellular morphology, which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice. Cyclopamine could effectively depress the expression of HHS proteins (Group C vs. Group B. F = 6.47, P < 0.05) and prevent tumor growth in nude mice (Group 2 vs. Group 1, t = 31.59, P < 0.01). Conclusions: The activity of HHS is upregulated during the CSE-induced malignant transformation of 16HBE cells. Cyclopamine can effectively depress expression of HHS proteins in vitro and prevent tumor growth of the transformed cells in vivo.
引用
收藏
页码:1191 / 1198
页数:8
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