title: DT-13 inhibits cancer cell migration by regulating NMIIA indirectly in the tumor microenvironment.
abstract: Tumor metastasis is one of the main causes of mortality among patients with malignant tumors. Previous studies concerning tumor metastasis have merely focused on the cancer cells in the tumor. However, an increasing number of studies show that the tumor microenvironment plays a vital role in the progression of cancer, particularly in tumor metastasis. Since fibroblasts and adipocytes are two of the most representative mesenchymal cells in the tumor microenvironment, we established a hypoxia-induced cancer-associated fibroblast (CAF) model and a chemically induced adipocyte model to reveal the effect of the microenvironment on cancer development. In these models, the conditioned medium from the tumor microenvironment was found to significantly promote the migration of human lung cancer cell line 95D and regulate the expression of non-muscle myosin IIA (NMIIA), which is consistent with results in the published literature. Then, we confirmed the hypothesis that the tumor microenvironment can regulate NMIIA in cancer cells and facilitate migration by using the non-muscle myosin II inhibitor, blebbistatin. Thus, this is the first report that the tumor microenvironment can promote cancer cell migration by regulating the expression of NMIIA. Our present data also indicated that DT-13, the saponin monomer 13 of dwarf lilyturf tuber, inhibited cancer cell migration in the tumor microenvironment model. Further results showed that DT-13 exhibited anti-migratory effects by inhibiting the c-raf/ERK1/2 signaling pathway. Consequently, our research confirmed that DT-13 significantly inhibited 95D cell migration in vitro, indicating the potential anti-metastatic effect of DT-13 on lung cancer and the scientific basis for drug development.
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Du
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Yu
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Sensen
authors.initials: S
authors.lastname: Lin
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wei
authors.affiliation: Tasly Research Institute, Tianjin Tasly Holding Group Co., Ltd., Tianjin 300410, P.R. China.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ghulam Jilany
authors.initials: GJ
authors.lastname: Khan
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D012503:Saponins; C578958:ruscogenin-1-O-(glucopyranosyl-(1-2))(xylopyranosyl-(1-3))fucopyranoside; C472645:blebbistatin; D019908:Proto-Oncogene Proteins c-raf; D018995:Myosin Heavy Chains