姜黄素联合治疗多药耐药Ht29结肠癌细胞系致敏

Abdul Rouf War
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引用次数: 2

摘要

结直肠癌已被证实是世界上第三大最可怕的癌症。最新的报告显示,由于饮食习惯,特别是食用高脂肪含量的食物,印度的结直肠癌正在以很高的速度增加。近年来,化疗已被认为是控制多种癌症的一种潜在治疗方法,如胃肠道癌症等。科学家们正在寻找一种新的药物来治疗癌症,以最小的毒性调节癌变过程。姜黄素是从姜黄中提取的一种植物化学物质。它是姜科姜黄根茎的高效制剂。它也被认为是癌症化疗治疗的一种有价值的药物。在动物研究中,已经明确提到姜黄素可以控制其他器官和结肠的癌变。姜黄素还具有抗诱变、抗炎的作用。也证实了姜黄素通过抑制COX-2的表达调控P-gp的表达。此外,姜黄素在多种细胞系中下调NF-kB通路,如Colo 205结肠癌细胞系等。多药耐药(MDR)在肿瘤细胞对多种化疗药物的细胞毒性产生耐药性中起着关键作用。癌细胞的这种特征是由于在反复暴露于药物的过程中,细胞内积累了低水平的化疗药物,表现出p -糖蛋白(MDR-1)的过度表达。p -糖蛋白是一种转运蛋白,它能使细胞排出多种化疗药物。最新报道表明COX-2表达与P-gp表达具有很强的相关性。在这项研究中,我们通过增加化疗药物盐酸多柔比星(DOX)的浓度来处理细胞,从而产生了多重耐药的HT29人结肠癌细胞,并进一步利用多柔比星积累试验来估计处理过的活细胞和死细胞的细胞内药物浓度。同时,每隔24小时分别观察DOX和姜黄素共处理(DOX+姜黄素)对HT29细胞形态学的影响。通过姜黄素联合治疗,观察姜黄素对多重耐药HT29结肠癌细胞的影响,进一步研究NFkB在mRNA和蛋白水平上控制的各种炎症基因,以及治疗后可能下调的细胞因子水平。本研究将有助于全面了解姜黄素在结肠癌中降低多药耐药(癌症的独特特性)作用的机制。
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Curcumin Co-Treatment Sensitizes Multi-Drug Resistant Ht29 Colon Cancer Cell Line
Colorectal cancer has been confirmed to be the third most dreadful cancer across the world. The latest reports show that the colorectal cancer is increasing in India at a high rate due to food habits, particularly consuming the foods with high fat content. Chemotherapy has been considered as a potential treatment in the control of a wide range of cancers recently, such as gastrointestinal cancers and so on. The scientists are looking to come up with new drugs to treat cancer by regulating the carcinogenesis with minimal toxicity. Curcumin is a phytochemical extracted from turmeric. It is highly effective product of the rhizomes of Curcuma longa L. (Zingiberaceae). It is also considered as a valuable drug for chemotherapeutic treatments in cancer. In case of animal studies, it has been clearly mentioned that curcumin controls carcinogenesis in various other organs as well as colon. Curcumin exhibits the capability to act as anti-mutagenic, anti-inflammatory drug as well. It has also been confirmed that the P-gp expression regulation is carried out by curcumin by inhibiting the COX-2 expression. Also, it has been clearly stated that curcumin down-regulates NF-kB pathway in various cell lines like Colo 205 colon cancer cell line etc. Multi Drug Resistance (MDR) plays a key role in case of the cancer cells to exhibit the resistance against the cytotoxicity of various chemotherapeutic drugs. This type of characteristics in cancer cells is developed due to low levels of the chemotherapeutic drug accumulated inside the cells during repeated exposure to the drug, showing the over-expression of P-glycoprotein (MDR-1). P-glycoprotein, a transporter protein, allows the cells to expel the wide range of chemotherapeutic drugs. The latest reports show that COX-2 expression and P-gp expression possess strong correlation with each other. In this research study, we generated the Multi-Drug Resistant HT29 Human colon cancer cells by treating the cells with increasing concentrations of a chemotherapeutic drug namely Doxorubicin Hydrochloride (DOX) and further we estimated the intracellular drug concentration in treated live as well as dead cells with the help of Doxorubicin Accumulation Assay. Also, the cell morphology change was studied in HT29 cells after every 24 hours of the DOX treatment separately as well as curcumin co-treatment (DOX+Curcumin). The curcumin co-treatment was carried out to observe the effect of curcumin on multi-drug resistant HT29 colon cancer cells and further study can be extended to investigate the various inflammatory genes controlled by NFkB at mRNA and protein level as well as the levels of cytokines which may get down-regulated by treatment. This study will help to completely understand the mechanism of reducing the effect of Multidrug Resistance (a unique property of cancer) by curcumin in case of colon cancer.
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