Tirbanibulin1%软膏是一种合成的抗增殖剂,于2021年被欧盟批准用于治疗光化性角化病(AK)。外用替尼布林已经临床解决了HPV-57(+)鳞状细胞癌(SCC),HPV-16(+)外阴高级别鳞状上皮内病变,疣状表皮发育不良,还有尖锐湿疣.我们研究了地尔巴尼布林如何影响HPV癌蛋白的表达,并影响参与细胞增殖和转化的其他细胞途径。我们处理了HeLa细胞系,含有整合的HPV-18,增加剂量的替尔巴尼布林,以确定对细胞增殖的影响。用针对Src经典途径的抗体进行免疫印迹,HPV18E6和E7转录调控,凋亡,以及侵袭和转移途径。用替班尼布林进行的细胞增殖测定确定HeLa细胞的半数最大抑制浓度(IC50)为31.49nmol/L。增加的地尔巴尼布林浓度下调Src的蛋白表达(p<0.001),磷酸-Src(p<0.001),ras(p<0.01),c-Raf(p<0.001),ERK1(p<0.001),磷酸化ERK1(p<0.001),磷酸化ERK2(p<0.01),phospho-Mnk1(p<0.001),eIF4E(p<0.01),磷酸-eIF4E(p<0.001),E6(p<0.01),E7(p<0.01),Rb(p<0.01),磷酸-Rb(p<0.001),MDM2(p<0.01),E2F1(p<0.001),磷酸FAK(p<0.001),phospho-p130Cas(p<0.001),Mcl-1(p<0.01),和Bcl-2(p<0.001),但上调CPARP(p<0.001),和cPARP/fPARP(p<0.001)。这些结果证明,替尼布林可通过Src-MEK-途径影响HPV癌蛋白的表达。Tirbanibulin显着下调与细胞周期调节和细胞增殖相关的致癌蛋白,同时上调凋亡途径。
Tirbanibulin是人类乳头瘤病毒(HPV)相关疾病的有希望的新疗法。Tirbanibulin1%软膏是一种经批准的用于治疗光化性角化病(AK)的合成局部软膏,皮肤癌的癌前病变.先前已报道局部使用的替尼布林可在临床上解决人乳头瘤病毒(HPV)-()疾病。在这项研究中,我们研究了替比尼布林如何影响与癌症相关的HPV和通路.我们处理HeLa细胞系以确定对HPV细胞增殖的影响。增加地尼布林的浓度在统计学上显着影响通常与癌症相关的许多细胞途径。这些结果证明,替尼布林可以影响HPV癌蛋白的表达,从而杀死癌细胞。
Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against the Src canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC50) of HeLa cells to be 31.49 nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src (p < 0.001), phospho-Src (p < 0.001), Ras (p < 0.01), c-Raf (p < 0.001), ERK1 (p < 0.001), phospho-ERK1 (p < 0.001), phospho-ERK2 (p < 0.01), phospho-Mnk1 (p < 0.001), eIF4E (p < 0.01), phospho-eIF4E (p < 0.001), E6 (p < 0.01), E7 (p < 0.01), Rb (p < 0.01), phospho-Rb (p < 0.001), MDM2 (p < 0.01), E2F1 (p < 0.001), phospho-FAK (p < 0.001), phospho-p130 Cas (p < 0.001), Mcl-1 (p < 0.01), and Bcl-2 (p < 0.001), but upregulates cPARP (p < 0.001), and cPARP/fPARP (p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.
Tirbanibulin is Promising Novel Therapy for Human Papillomavirus (HPV)-associated Diseases.Tirbanibulin 1% ointment is an approved synthetic topical ointment for treating actinic keratoses (AK), a precancer of skin cancer. Topical tirbanibulin has previously been reported to clinically resolve human papillomavirus (HPV)-( +) diseases.In this study, we examine how tirbanibulin may affect the HPV and pathways associated with cancer.We treated the HeLa cell line to determine the effects on HPV cell proliferation. Increasing the concentration of tirbanibulin statistically significantly affected numerous cellular pathways often associated with cancer.These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins and thereby kill cancer cells.