Isyraqiah Faizatul, K Kutty Methil, Durairajanayagam Damayanthi, Salim Norita, Singh Harbindarjeet
Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Malaysia.
Faculty of Medicine, Lincoln University College, Petaling Jaya 47301, Malaysia.
Exp Biol Med (Maywood). 2018 Oct;243(14):1118-1124. doi: 10.1177/1535370218813909. Epub 2018 Nov 17.
Leptin promotes the growth of gastric cancer cells . It is, however, unknown if leptin induces gastric cancer . This study therefore investigated the effect of leptin on the histology and expression of tumorigenic genes in the stomach of rats following 40 weeks of leptin treatment. Male Sprague-Dawley rats, aged 6 weeks, were randomized into control and experimental groups ( = 8 per group). The experimental group was given intraperitoneal injections of leptin (60 µg/kg/day) once daily for 40 weeks, whereas the control group received intraperitoneal injection of an equal volume of normal saline daily. Rats were housed in polypropylene cages for the duration of the study. Body weight was measured weekly. Upon completion of treatment, rats were euthanized and their stomachs were collected for histopathological examination, microarray, and RT-qPCR. Data were analyzed using one-way ANOVA and Fisher’s exact test. On histology, one rat (12.5%) in the leptin-treated group had a large red-colored tumor nodule at the pyloric antrum of the stomach. Microscopically, stomachs of two leptin-treated rats (25%) showed hyperplasia or dysplasia. Microarray analysis revealed significant upregulation of a number of genes in the stomachs of leptin-treated rats that have been shown to be associated with tumorigenesis in other tissues, including (protein maturation), and (translation factors), (vesicular trafficking), (plasma membrane trafficking), (protein degradation), and (oxygen transport), , , , and (cell migration), (signal transduction), and (transcription factors), and (oncogenes), (mRNA maturation), and (cell proliferation). None of the known oncogenes were, however, significantly up-regulated. In conclusion, although the overall effect of leptin on gastric carcinogenesis seems inconclusive, the findings of dysplasia and the up-regulation of some of the cancer-related genes nevertheless warrant further scrutiny on the role of leptin in gastric cancer.
Gastric cancer is the third most common cause of death due to cancer in the world. Obese individuals are at risk of developing gastric cancer, and the reason for this is unknown. Serum leptin levels are high in obese individuals and leptin is known to induce proliferation of gastric cancer cells . However, to date, no reports exist on the tumorigenic effects of leptin on the stomach . This study therefore determines if chronic leptin administration induces gastric carcinogenesis in non-obese rats, which might serve as a useful animal model for future studies. Although the findings are somewhat inconclusive, to our knowledge, however, this is the first study to show the up-regulation of numerous potential driver genes that highlight the potential role of leptin in the higher prevalence of gastric cancer among obese individuals. The findings certainly necessitate further scrutiny of leptin gastric cancer.
瘦素可促进胃癌细胞生长。然而，瘦素是否会诱发胃癌尚不清楚。因此，本研究调查了在对大鼠进行40周瘦素治疗后，瘦素对大鼠胃组织学及致瘤基因表达的影响。将6周龄的雄性斯普拉格-道利大鼠随机分为对照组和实验组（每组n = 8）。实验组大鼠每天腹腔注射一次瘦素（60 μg/kg/天），持续40周，而对照组大鼠每天腹腔注射等量生理盐水。在研究期间，大鼠饲养于聚丙烯笼中。每周测量大鼠体重。治疗结束后，对大鼠实施安乐死并收集其胃组织进行组织病理学检查、微阵列分析和逆转录定量聚合酶链反应（RT-qPCR）。数据采用单因素方差分析和费舍尔精确检验进行分析。组织学检查发现，瘦素治疗组中有1只大鼠（12.5%）在胃幽门窦处有一个大的红色肿瘤结节。显微镜检查显示，2只接受瘦素治疗的大鼠（25%）的胃出现增生或发育异常。微阵列分析显示，在接受瘦素治疗的大鼠胃中，许多已被证明与其他组织肿瘤发生相关的基因显著上调，包括（蛋白质成熟）、和（翻译因子）、（囊泡运输）、（质膜运输）、（蛋白质降解）、和（氧运输）、、、和（细胞迁移）、（信号转导）、和（转录因子）、和（癌基因）、（mRNA成熟）以及（细胞增殖）。然而，已知的癌基因均未显著上调。总之，尽管瘦素对胃癌发生的总体影响似乎尚无定论，但发育异常的发现以及一些癌症相关基因的上调仍值得进一步审视瘦素在胃癌中的作用。
胃癌是全球第三大常见癌症死因。肥胖个体有患胃癌的风险，但其原因尚不清楚。肥胖个体血清瘦素水平较高，且已知瘦素可诱导胃癌细胞增殖。然而，迄今为止，尚无关于瘦素对胃致瘤作用的报道。因此，本研究确定长期给予瘦素是否会在非肥胖大鼠中诱发胃癌，这可能为未来研究提供一个有用的动物模型。尽管研究结果有些不确定，但据我们所知，这是第一项显示众多潜在驱动基因上调的研究，突出了瘦素在肥胖个体胃癌患病率较高中可能发挥的作用。这些发现无疑需要对瘦素与胃癌的关系进行进一步审视。
