Interferon-β produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells.
Interferon-β produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells.
复制标题
DOI：
10.1371/journal.pone.0072709
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tagawa M
中科院分区：
文献类型：
--
作者：
Li Q;Kawamura K;Yang S;Okamoto S;Kobayashi H;Tada Y;Sekine I;Takiguchi Y;Shingyouji M;Tatsumi K;Shimada H;Hiroshima K;Tagawa M
干扰素 (IFN) 已在各种类型的恶性肿瘤中进行了治疗效果测试，但 IFN 成员的抗肿瘤作用机制和差异生物活性取决于各自的细胞类型。在这项研究中，我们检测了I型和III型干扰素对5种携带野生型p53基因的人间皮瘤细胞的生长抑制活性，结果表明，I型干扰素而不是III型干扰素会降低细胞活力。此外，与IFN-α治疗相比，IFN-β治疗的生长抑制活性和主要组织相容性复合物I类抗原的表达水平上调更大。细胞周期分析表明，I 型 IFN 增加了 S 期和 G2/M 期群体，以及随后的亚 G1 期部分。 IFN-β治疗的细胞周期变化也比IFN-α治疗更大，这些数据共同表明，IFN-β在间皮瘤中比IFN-α具有更强的生物活性。 I 型 IFN 处理的细胞增加了 p53 表达和磷酸化水平，并激活了细胞凋亡途径。 IFN-β与顺铂或培美曲塞（两者都是当前间皮瘤的一线化疗药物）的联合使用产生了协同抗肿瘤作用，亚G1期分数的增加也证明了这一点。这些数据首先证明，IFN-β通过上调p53表达与顺铂或培美曲塞对间皮瘤产生协同抗肿瘤作用。
Interferons (IFNs) have been tested for the therapeutic effects in various types of malignancy, but mechanisms of the anti-tumors effects and the differential biological activities among IFN members are dependent on respective cell types. In this study, we examined growth inhibitory activities of type I and III IFNs on 5 kinds of human mesothelioma cells bearing wild-type p53 gene, and showed that type I IFNs but not type III IFNs decreased the cell viabilities. Moreover, growth inhibitory activities and up-regulated expression levels of the major histocompatibility complexes class I antigens were greater with IFN-β than with IFN-α treatments. Cell cycle analyses demonstrated that type I IFNs increased S- and G2/M-phase populations, and subsequently sub-G1-phase fractions. The cell cycle changes were also greater with IFN-β than IFN-α treatments, and these data collectively showed that IFN-β had stronger biological activities than IFN-α in mesothelioma. Type I IFNs-treated cells increased p53 expression and the phosphorylation levels, and activated apoptotic pathways. A combinatory use of IFN-β and cisplatin or pemetrexed, both of which are the current first-line chemotherapeutic agents for mesothelioma, produced synergistic anti-tumor effects, which were also evidenced by increased sub-G1-phase fractions. These data demonstrated firstly to our knowledge that IFN-β produced synergistic anti-tumor effects with cisplatin or pemetrexed on mesothelioma through up-regulated p53 expression.
登录
查看更多内容
影响因子：
8.8
作者：
Halme, M;Knuuttila, A;Vehmas, T;Tammilehto, L;Mäntylä, M;Salo, J;Mattson, K
通讯作者：
Mattson, K
影响因子：
11.5
作者：
Sterman, Daniel H.;Recio, Adri;Albelda, Steven M.
通讯作者：
Albelda, Steven M.
影响因子：
64.8
作者：
Takaoka, A;Hayakawa, S;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
5.7
作者：
Fujie, Hitomi;Tanaka, Toshiaki;Numasaki, Muneo
通讯作者：
Numasaki, Muneo
影响因子：
4.8
作者：
Sandoval, R;Xue, JP;Colamonici, OR
通讯作者：
Colamonici, OR