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TRAIL可选择性、高效地诱导肿瘤细胞凋亡,虽然肺腺癌等部分肿瘤对TRAIL耐受,但其高效、低毒的优势吸引人们不断探索增敏策略。TRAIL与功能性受体DR4、DR5在细胞膜脂筏内组装为死亡诱导信号复合物(DISC);而诱骗受体DcR1和DcR2通过竞争结合TRAIL阻断凋亡。肺腺癌A549对TRAIL高度耐受,除DcR1外,MMP-2可能通过酶切跨膜型TRAIL的脱落而降低DISC组装,从而参与其耐药。阐明膜结合型TRAIL脱落机制可能为提高肺腺癌对TRAIL的敏感性提供新策略。
TRAIL can selectively and efficiently induce tumor cell apoptosis. Although some tumors such as lung adenocarcinoma are resistant to TRAIL, its high efficiency and low toxicity attract people to continuously explore sensitization strategies. TRAIL and functional receptors DR4 and DR5 are assembled as death-inducing signaling complex (DISC) in the lipid rafts of cells. The decoy receptors DcR1 and DcR2 block apoptosis by competitively binding TRAIL. Lung adenocarcinoma A549 is highly resistant to TRAIL. In addition to DcR1, MMP-2 may participate in its resistance to DISC by reducing shedding of transmembrane TRAIL. To elucidate the mechanism of membrane-bound TRAIL shedding may provide a new strategy for enhancing the sensitivity of lung adenocarcinoma to TRAIL.