title: Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway.
abstract: Integrin β1 facilitates cancer cell adhesion, migration and metastasis by activating intracellular signaling pathways including the ERK and PI3K signaling pathways. In previous studies, shikonin, an active naphthoquinone isolated from the Chinese medicine Zi Cao (gromwell), showed effective anticancer activity both in vivo and in vitro. However, the mechanisms underlying shikonin's anticancer activity are not fully elucidated. Increasing evidence indicates that shikonin inhibits tumor metastasis, but little is known about the effect of shikonin on lung cancer cells. To better understand the anti-metastatic role of shikonin in lung cancer, in this study we sought to investigate the effect of shikonin on lung cancer cell proliferation, adhesion to extracellular matrices (ECM), migration and invasion in non-small cell lung cancer A549 cells. We also sought to investigate the molecular mechanisms underlying shikonin's anticancer effects. Here we showed that when non-small cell lung cancer A549 cells were treated with shikonin for 24h, 8.0μM shikonin significantly inhibited cell proliferation, while cells treated with less than 2.0μM shikonin for 24h significantly suppressed cell adhesion to the ECM, invasion and migration in a dose-dependent manner. Moreover, real-time PCR and Western blot analysis showed that shikonin led to a reduction in the expression of integrin β1 at the mRNA and protein levels. Further elucidation of the mechanisms involved revealed that shikonin repressed the phosphorylation of extracellular signal-regulated kinase (ERK1/2). Taken together, our findings provide new evidence that shikonin suppresses lung cancer invasion and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway.
authors.affiliation: Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Rd, Shanghai 200433, PR China.
authors.forename: Heyong
authors.initials: H
authors.lastname: Wang
authors.forename: Chunlian
authors.initials: C
authors.lastname: Wu
authors.forename: Shengbang
authors.initials: S
authors.lastname: Wan
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhang
authors.forename: Songwen
authors.initials: S
authors.lastname: Zhou
authors.forename: Gentao
authors.initials: G
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019012:Integrin beta1; D009285:Naphthoquinones; C016101:shikonin