Knockdown of MADD and c-FLIP overcomes resistance to TRAIL-induced apoptosis in ovarian cancer cells.
Knockdown of MADD and c-FLIP overcomes resistance to TRAIL-induced apoptosis in ovarian cancer cells.
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DOI：
10.1016/j.ajog.2011.05.035
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发表时间：
2011-10
影响因子：
9.8
通讯作者：
Prabhakar BS
中科院分区：
文献类型：
--
作者：
Li LC;Jayaram S;Ganesh L;Qian L;Rotmensch J;Maker AV;Prabhakar BS
TRAIL在治疗已确定的人类恶性肿瘤中的临床效用受到对TRAIL耐药性的发展的限制。我们假设，MADD，一种TRAIL耐药因子的敲低，可以克服卵巢癌细胞中的TRAIL耐药。使用q-RT-PCR定量切除的卵巢癌标本和细胞系中的MADD表达。评估了卵巢癌细胞系对TRAIL的敏感性，有或没有MADD敲低。与正常卵巢组织相比，MADD在人恶性卵巢癌组织和细胞系中以相对较高的水平表达。OVCA 429和OVCAR 3对TRAIL敏感，CAOV-3和SKOV-3对TRAIL耐药。MADD在CAOV-3细胞中的敲低，而不是在SKOV-3细胞中，赋予TRAIL敏感性。SKOV-3细胞中c-FLIP的敲低增加了自发和TRAIL诱导的凋亡，这在MADD敲低后进一步增加。MADD/c-FLIPL敲低可使TRAIL抗性卵巢癌细胞对TRAIL敏感。
The clinical utility of TRAIL in the treatment of established human malignancies is limited by the development of resistance to TRAIL. We hypothesized that knockdown of MADD, a TRAIL-resistance factor, may overcome TRAIL resistance in ovarian cancer cells. MADD expression in resected ovarian cancer specimens and cell lines was quantified using q-RT-PCR. Sensitivity of ovarian cancer cell lines to TRAIL, with or without MADD knockdown was assessed. MADD is expressed at relatively higher levels in human malignant ovarian cancer tissues and cell lines compared to normal ovarian tissues. The cell lines OVCA429 and OVCAR3 were susceptible, and CAOV-3 and SKOV-3 were resistant to TRAIL. MADD knockdown in CAOV-3 cells, but not in SKOV-3 cells, conferred TRAIL sensitivity. Knockdown of c-FLIP in SKOV-3 cells increased spontaneous and TRAIL-induced apoptosis, which was further increased upon MADD knockdown. MADD/c-FLIPL knockdown can render TRAIL-resistant ovarian cancer cells susceptible to TRAIL.
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影响因子：
4.8
作者：
Li, Peifeng;Jayarama, Shankar;Prabhakar, Bellur S.
通讯作者：
Prabhakar, Bellur S.
影响因子：
5.2
作者：
Lee, Sung-Jun;Noh, Hyo-Jeong;Lee, Tae-Jin
通讯作者：
Lee, Tae-Jin
影响因子：
11.2
作者：
Liu, Xiangguo;Yue, Ping;Sun, Shi-Yong
通讯作者：
Sun, Shi-Yong
影响因子：
11.5
作者：
Herzog, TJ
通讯作者：
Herzog, TJ
影响因子：
8
作者：
Efimova, EV;Al-Zoubi, AM;Prabhakar, BS
通讯作者：
Prabhakar, BS