Brit J Cancer:低密度脂蛋白胆固醇能够抵消酪氨酸激酶抑制剂对肾细胞上皮癌的抗肿瘤活性

2017-04-06 AlexYang MedSci原创

酪氨酸激酶抑制剂(TKIs)治疗肾细胞上皮癌(RCC)可以提高病人的生存率。但是,大约1/4的肾细胞上皮癌病人用酪氨酸激酶抑制剂(TKIs)进行治疗时却很难治疗。最近,研究人员就低密度脂蛋白胆固醇对酪氨酸激酶抑制剂的抗肿瘤活性进行叶研究,期望能够初步解释酪氨酸激酶抑制剂进行治疗难治的原因。研究人员利用低密度脂蛋白胆固醇和酪氨酸激酶抑制剂分别或者一起处理肾细胞上皮癌细胞和内皮细胞,来检测肾细胞上皮癌

酪氨酸激酶抑制剂(TKIs)治疗肾细胞上皮癌(RCC)可以提高病人的生存率。但是,大约1/4的肾细胞上皮癌病人用酪氨酸激酶抑制剂(TKIs)进行治疗时却很难治疗。

最近,研究人员就低密度脂蛋白胆固醇对酪氨酸激酶抑制剂的抗肿瘤活性进行叶研究,期望能够初步解释酪氨酸激酶抑制剂进行治疗难治的原因。研究人员利用低密度脂蛋白胆固醇和酪氨酸激酶抑制剂分别或者一起处理肾细胞上皮癌细胞和内皮细胞,来检测肾细胞上皮癌细胞和内皮细胞的生存能力。另外,研究人员确认了PI3K/AKT信号通路在低密度脂蛋白胆固醇调控的酪氨酸激酶抑制剂抗性中的潜在作用。最后,研究人员同样也调查了高脂肪和高胆固醇饮食对肾细胞上皮癌异种种植肿瘤对舒尼替尼作用的影响。研究结果表明,低密度脂蛋白胆固醇的添加增加了PI3K/AKT信号通路的活性,并且妥协了酪氨酸激酶抑制剂对肾细胞上皮癌细胞和内皮细胞的抗肿瘤活性。更进一步的是,在高脂肪和高胆固醇喂养的小鼠中,肾细胞上皮癌异种种植肿瘤对酪氨酸激酶抑制剂表现为抵抗特性。最后,研究人员指出,在肾细胞上皮癌病人中,肾肿瘤维持它们自身的胆固醇稳态能力也许是对酪氨酸激酶抑制剂产生抗性的重要组成部分。

原始出处:

Sei Naito, Peter Makhov, Igor Astsaturov et al. LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma. British Journal of Cancer. 28 March 2017.  doi:10.1038/bjc.2017.77

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    2017-10-05 jklm09
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    2017-04-08 明天会更好!

    学习过了,很好!!!

    0

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    2017-04-07 redcrab
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