英國的一項新研究顯示，目前常用于治療艾滋病的藥物——洛匹那韋也有助于治療宮頸癌,，實驗顯示它可以有選擇地殺死即將癌變的細(xì)胞,，卻不會對正常細(xì)胞造成傷害。
英國曼徹斯特大學(xué)等機構(gòu)的研究人員在新一期英國《抗病毒療法》雜志上報告說,，洛匹那韋對由人類乳頭瘤病毒（HPV）引起的宮頸癌具有防治效果,。研究人員在實驗室中培養(yǎng)了人類細(xì)胞組織，結(jié)果發(fā)現(xiàn)洛匹那韋可殺死那些被HPV病毒感染且即將癌變的細(xì)胞,，但同時對那些未被感染的正常細(xì)胞卻沒有什么不良影響,。
研究人員伊恩·漢普森說，洛匹那韋已被證明是一種可安全口服的藥物,，不過本次研究顯示如果要對付HPV病毒,，用藥濃度可能需達(dá)到現(xiàn)在口服藥片所致濃度的10倍以上，這需要進(jìn)一步開展臨床研究加以確認(rèn),。
人類乳頭瘤病毒會造成皮膚或粘膜發(fā)生病變,，是宮頸癌的主要誘因之一，此外它還會導(dǎo)致口腔癌和喉癌等癌癥,。（生物谷Bioon.com）
生物谷推薦原文出處：
Antiviral Therapy doi: 10.3851/IMP1786
Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells
Gavin Batman, Anthony W Oliver, Ingeborg Zehbe, Christina Richard, Lynne Hampson, Ian N Hampson
Abstract
Background: We have previously shown that the HIV protease inhibitor lopinavir has selective toxicity against human papillomavirus (HPV)-positive cervical carcinoma cells via an unknown mechanism.
Methods: SiHa cervical carcinoma cells were stably transfected with the proteasome sensor vector pZsProSensor-1 to confirm lopinavir inhibits the proteasome in these cells. The Panorama Xpress profiler 725 antibody array was then used to analyse specific changes in protein expression in lopinavir-treated versus control untreated SiHa cells followed by PCR and western blotting. Colorimetric growth assays of lopinavir-treated E6/E7 immortalised versus control human keratinocytes were performed. Targeted small interfering RNA gene silencing followed by growth assay comparison of lopinavir-treated/untreated SiHa cells was also used.
Results: Lopinavir induced an increase in the fluorescence of pZsProSensor-1 transfected SiHa cells, indicative of proteasomal inhibition. Ribonuclease L (RNASEL) protein was shown to be up-regulated in lopinavir-treated SiHa cells, which was confirmed by PCR and western blot. Targeted silencing of RNASEL reduced the sensitivity of SiHa cells to lopinavir. Selective toxicity against E6/E7 immortalised keratinocytes versus control cells was also seen with lopinavir and was associated with up-regulated RNASEL expression.
Conclusions: These data are consistent with the toxicity of lopinavir against HPV-positive cervical carcinoma cells being related to its ability to block viral proteasome activation and induce an up-regulation of the antiviral protein RNASEL. This is supported by the drug’s selective toxicity and up-regulation of RNASEL in E6/E7 immortalised keratinocytes combined with the increased resistance to lopinavir observed in SiHa cells following silencing of RNASEL gene expression.
