Tirbanibulin 1% 软膏是一种合成抗增殖剂，于 2021 年获得欧盟批准用于治疗光化性角化病 (AK)。局部替巴尼布林已在临床上解决了 HPV-57 (  ) 鳞状细胞癌 (SCC)、HPV-16 (  ) 外阴高级鳞状上皮内病变、疣状表皮发育不良和尖锐湿疣。我们研究了替巴尼布林如何影响 HPV 癌蛋白表达以及影响细胞增殖和转化中涉及的其他细胞途径。我们用增加剂量的替巴布林处理含有整合型 HPV-18 的 HeLa 细胞系，以确定对细胞增殖的影响。使用针对 Src 经典途径、HPV 18 E6 和 E7 转录调控、细胞凋亡以及侵袭和转移途径的抗体进行免疫印迹。使用替巴尼布林进行细胞增殖测定，确定 HeLa 细胞的半数抑制浓度 (IC50) 为 31.49 nmol/L。增加替巴尼布林浓度可下调 Src (p < 0.001)、磷酸-Src (p < 0.001)、Ras (p < 0.01)、c-Raf (p < 0.001)、ERK1 (p < 0.001)、磷酸- ERK1（p < 0.001）、磷酸-ERK2（p < 0.01）、磷酸-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)、磷酸-p130 Cas（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)。这些结果证明替巴尼布林可能通过 Src-MEK-途径影响 HPV 癌蛋白的表达。替巴尼布林显着下调与细胞周期调节和细胞增殖相关的致癌蛋白，同时上调细胞凋亡途径。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

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.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.