In the treatment of unresectable advanced hepatocellular carcinoma (HCC), cisplatin is administered transhepatic arterially for local treatment, but the clinical application of cisplatin drugs is frequently hindered by the emergence of drug resistance. Kinesin family member 2C(KIF2C) has been shown as oncogene in a variety of tumors. Nevertheless, its effect on cisplatin sensitivity has yet to be ascertained. Herein, we aim to investigate the impact of the KIF2C gene on cisplatin sensitivity within HCC and the plausible underlying molecular mechanism. We examined the expression level of the KIF2C gene in HCC cells by real-time quantitative reverse transcription PCR and Western blot analysis, and analyzed bioinformatically by The Gene Expression Omnibus database and The Cancer Genome Atlas database. The KIF2C gene was silenced using the small interfering RNA technology, and its effect on cisplatin drug sensitivity in HCC cells was evaluated by flow cytometry, cell proliferation, cell migration, and invasion assays. Our results indicated that KIF2C was highly expressed in HCC cells. KIF2C silencing inhibits HCC cell proliferation, migration and invasion, promotes apoptosis, and keeps the cell cycle in G2 phase. In addition, KIF2C silencing enhanced the sensitivity of HCC cells to cisplatin. KIF2C silencing down-regulates the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mitogen-activated protein kinase 3 (MAPK3) proteins. In conclusion, KIF2C silencing amplifies the sensitivity of HCC cells to cisplatin by regulating the PI3K/AKT/MAPK signaling pathway. Consequently, targeting KIF2C shows great application potential as a strategy for enhancing the effectiveness of HCC treatment.

中文翻译：

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KIF2C沉默通过调节PI3K/AKT/MAPK信号通路增强肝癌细胞对顺铂的敏感性。

在不可切除的晚期肝细胞癌（HCC）的治疗中，顺铂经肝动脉给予局部治疗，但顺铂药物的临床应用常常因耐药性的出现而受到阻碍。驱动蛋白家族成员2C(KIF2C)已被证明是多种肿瘤中的癌基因。然而，其对顺铂敏感性的影响尚未确定。在此，我们的目的是研究 KIF2C 基因对 HCC 内顺铂敏感性的影响以及可能的潜在分子机制。我们通过实时定量逆转录PCR和蛋白质印迹分析检查了HCC细胞中KIF2C基因的表达水平，并通过基因表达综合数据库和癌症基因组图谱数据库进行生物信息学分析。采用小干扰RNA技术沉默KIF2C基因，通过流式细胞术、细胞增殖、细胞迁移和侵袭实验评估其对HCC细胞顺铂药物敏感性的影响。我们的结果表明 KIF2C 在 HCC 细胞中高表达。KIF2C沉默抑制HCC细胞增殖、迁移和侵袭，促进细胞凋亡，使细胞周期保持在G2期。此外，KIF2C沉默增强了HCC细胞对顺铂的敏感性。KIF2C 沉默下调磷脂酰肌醇 3-激酶 (PI3K)、蛋白激酶 B (AKT) 和丝裂原激活蛋白激酶 3 (MAPK3) 蛋白的表达水平。总之，KIF2C 沉默通过调节 PI3K/AKT/MAPK 信号通路增强 HCC 细胞对顺铂的敏感性。因此，靶向 KIF2C 作为增强 HCC 治疗有效性的策略显示出巨大的应用潜力。