脂質載運蛋白2在人類前列腺癌細胞之角色

西方國家，前列腺癌是男性最主要的癌症之一，也是造成男性死亡原因的第二位。大部分前列腺癌的產生與男性荷爾蒙有關，目前治療前列腺癌治療方式為荷爾蒙療法，手術，放射線治療…等。脂質載運蛋白-2 (LCN2)又稱嗜中性白血球明膠酶相關性脂質載運蛋白(NGAL)，屬於脂質載運蛋白家族成員之一，為25-kDa的分泌型蛋白質。許多文獻證實脂質載運蛋白-2與腫瘤生長、侵襲和凋亡扮演重要的功能，例如:乳癌、大腸癌和卵巢癌等等。但是，目前LCN2在人類前列腺癌細胞中的角色，至今仍不清楚。 本研究利用人類前列腺癌組織晶片以化學免疫染色法分析證實人類前列腺癌組織內LCN2蛋白表現比正常前列腺組織還高，且與病人的腫瘤期數和分化程度有關。此外我們也利用西方墨點法和全定量RT-PCR方式證實LCN2蛋白質和mRNA會大量表現在PC3和DU145細胞，但少量表現在LNCaP和22Rv細胞。為了更進一步證實LCN2在人類前列腺的生物功能，我們利用shRNA方式抑制PC3和DU145細胞內LCN2蛋白表現，也利用MTT方式和流式細胞儀證實抑制LCN2會抑制PC3和DU145細胞生長和誘導細胞週期停留G0/G1期。同時以細胞移動和侵襲實驗證實抑制LCN2會抑制PC3和DU145細胞移動與侵襲能力。利用動物異種移植模式證明當抑制LCN2可降低前列腺腫瘤的生長。綜合以上實驗結果說明LCN2在前列腺癌的增生與侵襲中扮演了一個重要的角色，且可當作前列腺癌進展的指標蛋白。

Prostate cancer (CaP) is one of the most common solid cancers among older men in Western countries, and it is also the second leading cause of cancer death among males. Most cases of prostate cancer progression are androgen-independent, and effective for the treatment of local prostate cancer by androgen ablation therapy, surgery, and radiation. Lipocalin-2 (also known as LCN2 and NGAL), which belongs to the superfamily of lipocalins, is identified originally as a 25-kDa secreted protein. It has an important role in the regulation of cellular oncogenesis and apoptosis. However, the role for LCN2 in prostate cancer remains unclear. LCN2 expression has been determined by Western blotting, qRT-PCR, and immunohistochemistry in the human prostate cell lines PC3, DU145, LNCaP, and 22Rv, and in human prostate tissue array. LCN2 protein and mRNA expression are higher in PC3 and DU145 cells than in LNCaP and 22Rv cells. In this study, we used shRNA-LCN2 to determine the role of LCN2 in prostate-cancer cell proliferation, migration, and invasion. Cell proliferative ability was measured by MTT, and cell-cycle analysis. The role of LCN2 in prostate-cancer cell migration and invasion was analyzed by cell-migration assay and Matrigel invasion assay. LCN2 knockdown in PC3 and DU145 cells decreased cell proliferation, colony formation, migration, and invasion, cell cycle arrest in G0/G1 phase. Subcutaneous xenografts in mice models showed decreased tumor growth in the LCN2-knockdown mice. Our results suggest that LCN2 might play an important role in regulation of proliferation and invasion of human prostate cancer, and that it can be a valuable marker of prostate cancer progression.