| Background: Tongue cancer is one of the most common malignant tumors in the oral and maxillofacial region.It is primarily squamous cell carcinoma with high malignant grade,fast growth and strong infiltration.Cervical lymph node metastasis occurs in the early stage of the disease.Furthermore,it is easy to relapse and has a poor prognosis,severely affecting the physical health and quality of human beings' life.At present,the major treatment means of tongue cancer involves combined and sequential therapy based on surgical extended resection of lesions combined with adjuvant radiotherapy and chemotherapy.Even so,the metforminastasis and recurrence rate is still high,constituting a key and difficult point of tongue cancer treatment.Adriamycin is commonly used broad spectrum antitumor drug in clinical practice,as well as a first-line chemotherapy drug for squamous cell carcinoma of the head and neck in clinical practice.Drug resistance is very likely to develop during its application in clinical chemotherapy,and the severity of the resulting adverse reactions increases with its dose,which limit the chemotherapeutic outcome of malignant tumor.Observations and researches in recent years have found that metformin which now has been widely used for the treatment of type II diabetic mellitus,has anti-tumor effect and high drug safety and good resistance.Relevant studies have indicated that the combination of metformin and many commonly-used chemotherapy drugs can not only reduce the dose of chemotherapy drug,but also achieve a good anti-tumor effect.Objective: The present research uses adriamycin and metformin to process human tongue cancer cells cultured in vitro to observe the effect of the combination of adriamycin and metformin and the single use of either on the invasion and migration and other aspects of human tongue cancer cell line SCC-15,to explore its potential mechanism and provide theoretical foundation for the drug use of postoperative chemotherapy of tongue cancer patients in the hope of improving the postoperative survival rate of tongue cancer patients.Methods: Human tongue cancer SCC-15 cells were cultured in normal conditions in vitro.The experimental groups were given adriamycin alone,metformin alone and adriamycin and metformin for intervention,while the control group was given no drug treatment.MTT metforminhod was used to detect the influences on the cell viability of the control group and each experimental group.Plate clone formation experiment was conducted to the in vitro clone formation capability.Transwell invasion chamber experiment was performed to observe the invasion capacity of these cells in the control group and each experimental group.Scratch-healing experiment was carried out to observe the transfer capacity of these cells in the control group and each experimental group.q RT-PCR was performed to detect and compare the expression levels of matrix metforminalloproteinase MMP-2 and MMP-9 m RNA of the control group and each experimental group.Result:1.The survival rate of human tongue cancer SCC-15 cells decreased gradually with the increase of adriamycin or metformin concentration.Compared with the control group,the F values of the groups processed at different adriamycin concentrations at 24 h,48h and 72 h were 97.641,115.999 and 128.524 respectively(P<0.01);the F values of the groups processed at different metformin concentrations at 24 h,48h and 72 h were 152.638,293.524 and 279.923(P<0.01).Compared with the single use of adriamycin or metformin,the combined use of the two could more obviously lower the viability of SCC-15 cells,showing statistically significant differences(t values were-10.892 and-6.311,respectively,P <0.01).2.Both adriamycin and metformin could inhibit the clone formation capacity of SCC-15 cancer cells in vitro,Compared with the control group,t values were-6.242 and-14.519 respectively(P<0.05).Compared with the single use of adriamycin or metformin,the combined use of the two could inhibit the in vitro clone formation capacity of SCC-15 cancer cells more obviously,and t values were-21.354 and-13.610 respectively(P<0.01).3.Compared with the control group,0.05mg/L adriamycin(ADM)in vitro condition could improve the invasion and migration of human tongue cancer SCC-15 cells(t=3.395 and 4.881,P<0.05);5mmol/L metformin(MET)could inhibit the invasion and migration of human tongue cancer SCC-15 cells(t=-4.593 and-7.273,P<0.05).Compared with the single use of adriamycin or metformin,the combined use of the two(0.05 mg/L ADM + 5 mmol/L MET)could inhibit the invasion and migration of human tongue cancer SCC-15 cells more obviously(t=-18.908 and-23.655,and t=-5.191 and-6.592,P<0.01).4.Compared with the control group,the relative expression quantities of MMP-2 and MMP-9 m RNA in the cells of the groups processed with adriamycin were increased(t=32.659 and 43.246,P<0.01);the relative expression quantities of MMP-2 and MMP-9 m RNA in the cells of the groups processed with metformin were obvious lowered(t=-23.989 and-32.217,P<0.01).Compared with the single use of adriamycin or metformin,the relative expression quantities of MMP-2 and MMP-9 m RNA in the cells of the group with the combined use of the two were obviously lowered(t=-33.352 and-6.669,and t=-67.214 and-29.973,P<0.01).Conclusions: 1.Both adriamycin and metformin could inhibit the growth of SCC-15 cells and show time-concentration dependency within a certain concentration range.The combined use of the two drugs had a more obvious effect.2.Metformin could inhibit the invasion and migration of human tongue cancer SCC-15 cells,and the inhibition effect of the combined used of adriamycin and metformin were more obvious;its major mechanism might be that drug action influenced the expression of relevant genes. |
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