To investigate the effect of caveolin-1 on invasion and metastasis of human breast carcinoma Hs578T doxorubicin-resistanted cells, Hs578T/Dox+cav-1 was as experiment group which up-regulated caveolin-1 by introducing the pCI-neo caveolin-1 gene, and Hs578T/Dox+vector introduced the pCI-neo vector was as controlled group. It was revealed that caveolin-1 in Hs578T/Dox cells is an important factor for mediating filopodia formation, which may enhance the invasive of cells. Hs578T/Dox+cav-1 cell formed long and abundant pseudopodia and only few filopodia were detectable in Hs578T/Dox+vector cells. It was shown that adhesive capability of Hs578T/Dox cells enhanced with up-regulated expression of caveolin-1 protein(P<0.01). Introducing the caveolin-1 gene into Hs578T/Dox cells enhanced their migration and invasive capability, as revealed by an in vitro chamber invasion assay(P<0.01). Apoptosis index of Hs578T/Dox+cav-1 group resulting from loss of cell-matrix interactions decreased comparing Hs578T/Dox+vector group(P<0.01). Caveolin-1 inhibited anoikis of Hs578T/Dox cells and that allowed survival of cancer cells during systemic circulation, thereby facilitating secondary tumor formation in distant organs. The efficacy in vivo of caveolin-1 was tested using cells xenografted into nude mice. Each mouse in both fifteen-mice groups were hypodermically injected with equivalent doses of 5×105 cells from Hs578T/Dox+cav-1 or Hs578T/Dox+vector. Tumors in Hs578T/Dox+cav-1 group were all formed after injection followed for 4 weeks, while no one in Hs578T/Dox+vector group. Lung metastasis was found in one mouse injected Hs578T/Dox+cav-1 cells. In conclusion, up-regulated caveolin-1 level in Hs578T doxorubicin-resistanted cells markedly elevates their capacity to tumor invasion and metastasis.
ZHENG Ya-Min, LI Fei, QI Bao-Ju, WU Ping, SUN Hai-Chen, LIU Shuang, CHEN Jian-Wen. Promotion of Invasion and Metastasis in Human Breast Carcinoma Hs578T/Dox by Caveolin-1[J]. Progress in Biochemistry and Biophysics,2007,34(1):25-30
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