Xi-ran He¹, Shu-yan Han², Wen-xian Zheng²

¹Department of Integration of Traditional Chinese and Western Medicine, Peking University Cancer Hospital & Institute, ²Peking University Cancer Hospital.

Objective:Traditional Chinese medicine Bu-FeiDecoction (BFD) containing six species of herbs has been used to treat lung cancer patients with Qi deficiency for thousands of years, and BFD indeed prolonged survival and improved quality of life according to previous clinical experience. Nevertheless, little is known about its potential mechanisms sofar. Herein, the present study was designed to explore whether BFD antagonized epithelial-mesenchymal transition (EMT) via blocking TGF-β1-induced signaling pathway, then to creating a relatively steady microenvironment for confining lung cancer. Method: This experiment was performed in vitro and in vivo by lung adenocarcinoma A549 cells. In detail, the influences on migration andinvasion were detected by wound healing and trans well assays, the cell morphological alterations mediated by TGF-β1 were monitored by a inverted phase-contrast microscope, and the effects of BFD on cell viability were evaluated by CCK-8 assays. Relevant protein and gene levels including E-cadherin, N-cadherin, vimentin, fibronectin, snail, slug, twist, smad2/3,TGF-β1, etc, were determined by Western blotting, confocal microscopy, quantitative real-time polymerase chain reaction, IHC and ELISA, etc. Withrespect to animal trials, female BALB/C nude mice were subcutaneously implanted A549 cell, and were given BFD by gavage (equivalent to 8 times dosage ashuman). Tumor volume, protein expressions associated with EMT and TGF-β1 inserum were evaluated, respectively. Result: Through functional assays, Western blotting, qRT-PCR, confocal microscopy, IHC, ELISA, etc, the data elucidated that BFD could dose-dependently suppress EMT induced by TGF-β1 invitro, via attenuating canonical Smad signaling pathway, while exerted noeffect on cell proliferation. And referring to animal trials, tumor growth could not be restrained, BFD inhibited protein markers associated with EMT andTGF-β1 secretion into serum through Western blotting, IHC and ELISA. Conclusion:Taken together these above data, the conclusion could be put forward that BFD attenuated EMT of non-small cell lung cancer via inhibition of canonical Smad signaling pathway mediated by TGF-β1 in vitro and in vivo, then to maintain the steady states of A549 cells and confine it to some extent. Therefore, BFD could be regarded as an efficacious adjuvant chemotherapeutic candidate with great promise for lung cancer patients.

Key Words: Tumor microenvironment  Transforming growth factor