吉非替尼能诱导宫颈癌细胞发生厌氧反应。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-02-01
Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Yoon Suk Kim
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引用次数: 0

摘要

吉非替尼对肺癌、卵巢癌、乳腺癌和结肠癌等多种癌症具有抗癌作用。然而,吉非替尼对宫颈癌的治疗效果及其内在机制仍不清楚。因此,本研究旨在探讨吉非替尼是否可用于治疗宫颈癌,并阐明其潜在机制。结果显示,吉非替尼能诱导卡巴酶依赖性的HeLa细胞凋亡,从而使细胞变圆并脱离培养板表面。吉非替尼诱导肌动蛋白细胞骨架的重组,并下调p-FAK、整合素β1和E-cadherin的表达,而这三种蛋白分别在细胞-细胞外基质粘附和细胞-细胞相互作用中起重要作用。此外,吉非替尼阻碍了细胞的再粘附和扩散,抑制了悬浮液中脱落细胞之间的相互作用,导致聚(ADP-核糖)聚合酶裂解,这是细胞凋亡的标志。它还能诱导另一种宫颈癌细胞系 C33A 细胞发生脱落诱导凋亡(anoikis)。综上所述,这些结果表明吉非替尼会引发宫颈癌细胞的anoikis。我们的研究结果可作为扩大用于治疗宫颈癌的抗癌药物范围的依据。
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Gefitinib induces anoikis in cervical cancer cells.

Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimed to explore whether gefitinib can be used to treat cervical cancer and elucidate the underlying mechanisms. Results showed that gefitinib induced a caspase-dependent apoptosis of HeLa cells, which consequently became round and detached from the surface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression of p-FAK, integrin β1 and E-cadherin, which are important in cell-extracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells in suspension, leading to poly (ADP-ribose) polymerase cleavage, a hallmark of apoptosis. It also induced detachment-induced apoptosis (anoikis) in C33A cells, another cervical cancer cell line. Taken together, these results suggest that gefitinib triggers anoikis in cervical cancer cells. Our findings may serve as a basis for broadening the range of anticancer drugs used to treat cervical cancer. [BMB Reports 2024; 57(2): 104-109].

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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