The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, PR China.
Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, PR China.
Life Sci. 2019 May 1;224:255-262. doi: 10.1016/j.lfs.2019.03.065. Epub 2019 Mar 27.
To understand potential pro-oncological effects of lower dose paclitaxel treatment in cervical cancer cells, we investigated the potential roles of KRT17 on migration and proliferation of cervical cancer cells which might respond to cytoskeletal-based drugs treatments.
We extracted the clinic data of cervical cancer patients from TCGA database to investigate mRNA expression of different keratins. HPV genotypes were identified by reverse transcription PCR. krt17 mRNA and EMT markers were quantified by real-time PCR. krt17 and EMT markers protein were immunoblotted by western blot. Cell viability was detected by CCK8. Cell migration was performed by transwell migration assay.
Our results showed that HPV16 infection correlated with the expression of KRT17 in cervical cancer cell lines. KRT17 knockdown would decrease Snail2 and elevate E-Cadherin to inhibit migration of Caski cells and SiHa cells. Lower dose of paclitaxel promoted SiHa proliferation, it also significantly promoted the migration of Caski cells. Otherwise, colchicine and higher dose of paclitaxel dose-dependently suppressed the proliferation and migration of Caski cells and SiHa cells. Moreover, KRT17 knockdown significantly facilitated cytoskeletal-based drugs to inhibit migration and induce cytotoxicity in cervical cancer cells.
KRT17 played pivotal oncogenic roles in cell survival, migration and paclitaxel-induced resistance of cervical cancer cells. Thus, KRT17 would serve as a promising target for compromising paclitaxel-induced resistance and metastasis.
为了了解低剂量紫杉醇治疗宫颈癌细胞中潜在的致癌作用，我们研究了 KRT17 对宫颈癌细胞迁移和增殖的潜在作用，这些细胞可能对细胞骨架药物治疗有反应。
我们从 TCGA 数据库中提取了宫颈癌患者的临床数据，以研究不同角蛋白的 mRNA 表达。通过反转录 PCR 鉴定 HPV 基因型。通过实时 PCR 定量测定 krt17 mRNA 和 EMT 标志物。通过 Western blot 免疫印迹测定 krt17 和 EMT 标志物蛋白。通过 CCK8 检测细胞活力。通过 Transwell 迁移实验进行细胞迁移。
我们的结果表明，HPV16 感染与宫颈癌细胞系中 KRT17 的表达相关。KRT17 敲低会降低 Snail2 并升高 E-钙粘蛋白，从而抑制 Caski 细胞和 SiHa 细胞的迁移。低剂量紫杉醇促进 SiHa 增殖，也显著促进 Caski 细胞的迁移。另一方面，秋水仙碱和高剂量紫杉醇剂量依赖性地抑制 Caski 细胞和 SiHa 细胞的增殖和迁移。此外，KRT17 敲低显著促进了细胞骨架药物抑制宫颈癌细胞迁移并诱导细胞毒性。
KRT17 在宫颈癌细胞的存活、迁移和紫杉醇诱导的耐药中发挥着关键的致癌作用。因此，KRT17 可以作为克服紫杉醇诱导的耐药性和转移的有前途的靶点。
