بررسی اثر مرفین و ترکیب آن با نالوکسان، مهارکننده گیرنده کانابینوئید نوع 1 (Am251)، مهار کننده فسفولیپاز (U73122) و پرگابالین بر زنده مانی سلول‌های سرطانی مری YM1

محورهای موضوعی : فصلنامه زیست شناسی جانوری

حسین محمدپور کارگر ¹ (گروه زیست شناسی، واحد دامغان، دانشگاه آزاد اسلامی، دامغان، ایران)
مهیار انصاری ² (گروه زیست شناسی، واحد دامغان، دانشگاه آزاد اسلامی، دامغان، ایران)

تاریخ دریافت : 1402/08/19 تاریخ پذیرش : 1403/03/12 تاریخ انتشار : 1403/05/16

کلید واژه: رده سلولی سرطان مری YM1, مورفین, نالوکسان, Am251, U73122, پرگابالین,

چکیده مقاله :

مشخص شده است که مورفین می‌تواند غیر از اثر بی¬دردی، بر تکثیر سلول‌های سرطانی مری نیز اثر گذار باشد. در این مطالعه اثر مورفین، نالوکسان، به همراه مهار کننده گیرنده کانابینوئید نوع 1 (Am251)، مهار کننده فسفولیپاز (U73122) و پرگابالین بر روی رده سلولی سرطان مری YM1 ارزیابی گردید. سلول‌های رده سلولی سرطان مری YM1در محیط کشت RPMI-1640 ﺣﺎﻭﻱ ۱۰ ﺩﺭﺻﺪ FBS تکثیر شدند. سپس سلول‌ها با غلطت¬های مختلف داروها به مدت 24 ساعت تیمار شده و میزان زنده ماندن سلول‌ها به روش MTT تعیین گردید. تجزیه و تحلیل نتایج به روش one way ANOVA و آزمون تعقیبی LSD انجام شد. بررسی‌های انجام شده نشان داد که مورفین در هر سه دوز (87، 175 و350 میکرومولار) میزان بقای سلول‌ها را به طور معنی‌داری کاهش می¬دهد (05/0 p <). افزودن نالوکسان 60 میکرومولار به محیط کشت نتوانست میزان بقای سلول‌های سرطانی مری را تغییر دهد. اما نالوکسان به همراه مورفین350 میکرومولار میزان بقا را به طور معنی‌داری نسبت به گروه کنترل (001/0 p <) و گروه نالوکسان کاهش داد (02/0 p <). مهار فسفولیپاز C با U23177 با غلظت 1 میکرومولار به تنهایی (001/0 p <) و یا همراه مورفین 350 میکرومولار میزان بقای سلول‌ها را (001/0 p <) کاهش داد. همچنین AM251 با غلظت 140 میکرومولار به تنهایی (05/0 p <) و یا همراه با مورفین 350 میکرومولار میزان بقا را (001/0 p <) کاهش داد. پر گابالین با غلظت 6 میکرومولار به تنهايي (05/0 p <) و یا همراه با مورفین 350 میکرومولار زنده¬مانی سلول‌ها را نسبت به گروه کنترل (001/0 p <) و نسبت گروه مورفین 350 میکرومولار کاهش داد (01/0 p <). همچنین در گروهی که در معرض هر سه ترکیب قرار گرفته بود بقا سلول‌ها بشدت (001/0 p <) کاهش یافت. نتایج نشان داد که مورفین و داروهای مورد بررسی در این مطالعه می‌توانند به عنوان گزینه‌های بالقوه برای کاهش رشد سلولی در بیماران مبتلا به سرطان پیشرفته مری مورد استفاده قرار گیرند.

چکیده انگلیسی:

It has been found that morphine may affect proliferation of cancer cells in addition to the effect of analgesia. In this study, the effects of morphine, naloxone, cannabinoid receptor type 1 inhibitor (Am251), phospholipase C inhibitor (U73122) and pregabalin were evaluated on YM1 esophageal cancer cell line viability. Esophageal cancer cell line YM1 cells were propagated in RPMI-1640 medium containing 10% FBS. Then the cells were treated with different doses of drugs for 24 hours and the cell viability was determined by the MTT method. The results were analyzed by one-way ANOVA and LSD post hoc test. The investigation showed that morphine in all three doses (87, 175 and 350 μM) significantly reduced the viability of cells (p < 0.05). The addition of 60 μM naloxone to the culture medium could not change the survival rate of esophageal cancer cells. But naloxone along with 350 μM morphine significantly decreased the survival rate compared to the control group (p < 0.001) and the naloxone group (p < 0.02). Phospholipase C inhibitor (U23177, 1mM) alone (P < 0.001) or together with 350 µM morphine decreased cell viability (p < 0.001). Also, AM251 140 μM alone (p < 0.05) or together with morphine decreased cell viability (p < 0.001). Pergabalin with a concentration of 6 μM with 6 mM alone (p < 0.05) or together with morphine decreased cell viability compared to the control group (p < 0.001) and the ratio of the 350 μM morphine group (p < 0.01). Also, cell viability in the group that was exposed to all three compounds was greatly reduced (p < 0.001). The results showed that morphine and the drugs investigated in this study can be used as potential options to reduce cell growth in patients with advanced esophageal cancer.

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