Abstract
Lung cancer is one of the most common malignancies worldwide. Actinidia chinensis Planch root extract (acRoots) was found to have the capacity of the anti-tumor, although the molecular mechanisms remain unclear. The present study aims to investigate the molecular mechanisms by which lung cancer cells sense to inhibitory effects of acRoots with a special focus on immune-associated gene profiles. We firstly provide a preclinical evidence that acRoots can significantly inhibit lung cancer cell proliferation and apoptosis via the PI3K-OASL signal pathway. The heterogeneous alterations of immune-associated gene profiles of lung cancer cell types were measured after treatment with various doses of acRoots. The OASL gene was identified as the key regulator in molecular networks of acRoots-treated lung cancer cells and validated. The OASL gene plays an important role in the regulation of lung cancer cell sensitivity to acRoots, which modulated by the PI3K signal pathway. Thus, our data indicate that OASL can be one of the decisive regulators to maintain lung cancer cell susceptibility to acRoots and may be associated with the development of drug resistance. The regulation of OASL can be an alternative strategy to improve drug efficacy during cancer therapies.
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Funding
The work was supported by the Zhongshan Distinguished Professor Grant (XDW), the National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81300010), the Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600, 14431905100), the Operation funding of Shanghai Institute of Clinical Bioinformatics, the Ministry of Education for Academic Special Science and Research Foundation for PhD Education (20130071110043), and the National Key Research and Development Program (2016YFC0902400, 2017YFSF090207).
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Supplement Figure 1
Chemical structure of 2β, 3β, 23-trihydroxy-urs-12-ene-28-olic acid (A) and 2α, 3α, 19α, 23, 24-pentahydroxyurs-12-en-28-oic acid (B). (GIF 9.02 kb)
Supplement Figure 2
Select a valid small interference sequence. And verify OASL siRNA-1176 on lung cancer cell proliferation. (A) The mRNA level of OASL was evaluated after treated with different OASL siRNA which were provided by biological company. (B) H460 cells proliferation was measured after treated with OASL siRNA-1176. (GIF 36.9 kb)
Supplement Figure 3
Response of OASL downstream inflammatory genes after inducing by acRoot. The mRNA level of IL-8 (A) and IL-12 (B) was measured after treated with 1, 5, 10 mg/ml acRoots and OASL siRNA-1176. (GIF 40.9 kb)
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Lv, J., Wang, L., Shen, H. et al. Regulatory roles of OASL in lung cancer cell sensitivity to Actinidia chinensis Planch root extract (acRoots). Cell Biol Toxicol 34, 207–218 (2018). https://doi.org/10.1007/s10565-018-9422-4
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DOI: https://doi.org/10.1007/s10565-018-9422-4