Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
Mol Biol Rep. 2012 Mar;39(3):3029-35. doi: 10.1007/s11033-011-1065-y. Epub 2011 Jun 16.
Bone is one of the most frequent targets of small cell lung cancer (SCLC) metastasis, but the molecular mechanism remains unclear. β3-integrin plays an important role in invasion of various kinds of tumors. Yet, its role in bone-metastasis of SCLC is still unknown. In this study, we first examined the expression of β3-integrin in SBC-5 and SBC-3 cells by real-time PCR, western blot and immunofluorescence. We found that, compared to none bone-metastatic SBC-3 cells, β3-integrin was highly expressed in SBC-5 cells, a specific bone-metastatic SCLC cells line characterized in our previous study. We next constructed β3-integrin siRNA and transfected SBC-5 cell line, and found that β3-integrin siRNA significantly down-regulated the β3-integrin mRNA level and protein expression in SBC-5 cell line. We further found that inhibition of β3-integrin significantly reduced tumor cell proliferation and induced apoptosis. In addition, the β3-integrin down-regulated cells presented significant decrease in cell adhesion, migration and invasion activity. Our results suggest the β3-integrin has an essential effect on tumor cell proliferation and progression, and may be a potential therapeutic target for the prevention of skeletal metastases of lung cancer.
骨骼是小细胞肺癌（SCLC）转移的最常见靶点之一，但分子机制尚不清楚。β3-整合素在各种肿瘤的侵袭中发挥重要作用。然而，其在 SCLC 骨转移中的作用尚不清楚。在这项研究中，我们首先通过实时 PCR、western blot 和免疫荧光法检测了 SBC-5 和 SBC-3 细胞中β3-整合素的表达。与无骨转移的 SBC-3 细胞相比，β3-整合素在 SBC-5 细胞中高度表达，SBC-5 细胞系是我们之前研究中具有特异性骨转移的 SCLC 细胞系。我们接下来构建了β3-整合素 siRNA 并转染 SBC-5 细胞系，发现β3-整合素 siRNA 显著下调了 SBC-5 细胞系中β3-整合素的 mRNA 水平和蛋白表达。我们进一步发现，抑制β3-整合素显著降低了肿瘤细胞的增殖并诱导了细胞凋亡。此外，β3-整合素下调的细胞黏附、迁移和侵袭活性显著降低。我们的结果表明，β3-整合素对肿瘤细胞的增殖和进展有重要影响，可能是预防肺癌骨转移的潜在治疗靶点。
