Background: Oral Squamous Cell Carcinoma (OSCC) is a major sub-type of oral cancer that shares 90% proportion of oral cavity cancers. It is declared as the sixth most frequent cancer among all cancer types throughout the world. Higher morbidity in Asian countries is reported due to frequent use of Smokeless Tobacco (SLT) products besides exposure to other risk factors. Hyperactivation of epidermal growth factor receptors is a molecular event in many solid tumors including oral cancer making them potential therapeutic targets.

Objective: Current study was designed to explore the effect of varlitinib, a pan-HER inhibitor, on oral cancer cell line. We investigated key regulatory genes in downstream pathway in response to drug treatment. Furthermore, we also examined expression profile of these genes in malignant and healthy oral tissue.

Methods: Gene expression pattern in drug treated and untreated cancer cell line along with OSCC tumor samples (n=45) and adjacent normal tissues was studied using real time PCR.

Results: In response to varlitinib treatment, significant suppression of oncogenes (IGF1R, MAPK1, SFN and CDK2) was observed. Interestingly, mRNA expression level of CDKN1A and Akt1 was found to be the opposite of what was expected. In case of malignant tissue, over expression of oncogenes (IGF1R, Akt1, MAPK1, SFN and CDK2) with simultaneous down expression of tumor suppressor genes (Tp53 and CDKN1A) was noted. STRING analysis indicated a strong association among differentially expressed genes suggesting their combined role in carcinogenesis.

Conclusion: In summary, our results indicate that varlitinib can be considered as a potential therapeutic agent in oral cancer due to its antitumor potential.

中文翻译：

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Varlitinib通过下调MAPK / EGFR途径介导口腔癌的活性

背景：口腔鳞状细胞癌（OSCC）是口腔癌的主要亚型，占口腔癌的90％。在全世界所有癌症类型中，它被宣布为第六常见的癌症。据报道，亚洲国家的发病率更高，这是由于除接触其他危险因素外，还经常使用无烟烟草（SLT）产品。表皮生长因子受体的过度活化是许多实体瘤（包括口腔癌）中的分子事件，使其成为潜在的治疗靶标。

目的：目前的研究旨在探讨泛HER抑制剂varlitinib对口腔癌细胞系的作用。我们调查了下游途径对药物治疗的关键调控基因。此外，我们还检查了这些基因在恶性和健康口腔组织中的表达谱。

方法：使用实时荧光定量PCR研究药物治疗和未治疗的癌细胞系以及OSCC肿瘤样品（n = 45）和邻近正常组织中的基因表达模式。

结果：响应瓦利替尼治疗，观察到显着抑制癌基因（IGF1R，MAPK1，SFN和CDK2）。有趣的是，发现CDKN1A和Akt1的mRNA表达水平与预期的相反。在恶性组织的情况下，注意到癌基因（IGF1R，Akt1，MAPK1，SFN和CDK2）的过度表达，同时抑癌基因（Tp53和CDKN1A）的表达却下降。STRING分析表明差异表达的基因之间有很强的联系，表明它们在致癌作用中起着联合作用。

结论：总而言之，我们的结果表明瓦利替尼具有抗肿瘤潜力，可以被认为是口腔癌的潜在治疗剂。