Establishing Of Sorafenib Resistant Renal Cancer Cell Line And Clinical Investigation In Patients With Advanced Renal Cell Carcinoma Sorafenib Drug Resistant

Objective:At present, molecularly targeted drugs, such as sorafenib, brings a dawn for the treatment of advanced renal carcinoma. However, some patients is resistance to molecularly targeted drugs at the very beginning, and the initial effective patient also gradually acquired resistance. All these are greatly affected the efficacy of molecularly targeted drugs. This subject design experiments to establish renal carcinoma cell line which is resistant to sorafenib. In order to further explore the mechanism of drug resistance, to guide the clinical medication, prolong the life of patients. And takes a retrospective study of our hospital’s clinical data of taking sorafenib for renal carcinoma treatment, The analysis of the present situation of its drug resistance and drug resistance may be the cause.Methods:Experiment: To establish the research of sorafenib-resistant renal carcinoma cell lines. We divided Human renal cell carcinoma cell line 786-O in two groups, A group is incubate by 1640 medium with 10% FBS,B group is incubate by 1640 medium with 10% FBS was added Sorafenib 0.01μmol / L,two groups both incubate in 5%CO2、37℃incubator,After several passages groups measured by MTT assay IC50 values,multiple drug resistance according to a formula. Multiples of more than 25 drug resistant cell lines established successfully.Clinical Investigation: To retrospective analysis of 95 cases which is treated by sorafenib and For a complete follow-up clinical and pathological data from October 2007 to October 2013, there are 74 male cases and 21 female cases, The average age is 61(Median 60; range is from 27 to 85 years old). In all these 95 cases, there are 86 cases of Clear cell carcinoma with Chromophobe cell carcinoma, 1 cases of Chromophobe renal carcinoma, 2 cases of Papillary carcinoma,1 cases of Clear cell carcinoma with Chromophobe cell carcinoma,5 cases of Pathological type unknown. In all these cases, The average survival time is 26 months(Median 20 months; range is from 3 to 81 months)。There are 17 drug resistance patients which accounts for 18 percent in total number and the average survival time is about 16 months. There are 78patients who do not has drug resistant problem and the average survival time is about 28 months. Based on the analysis of Clinical data, pathological data and long-term follow-up data,analyze the causes resistanceand and use the Kaplan-Meier survival function, we are going to compare the differences between the two groups of patients with or without long-term survival.Results:Experiment: measured by MTT assay is sensitive to the wavelength of 490 nm and drug groups at OD values calculated after two IC50 of sensitive groups 0.009μmol / L, resistant group 0.289μmol / L. Into the formula: drug multiple = resistant cell IC50 value / sensitive cells IC50 values. Regarded as a multiple of approximately 32.11 resistance. Multiples of more than 25 drug resistant cell lines established.Clinical research: 95 patients in this survey the average survival time of 26 months, of which 17 were resistant to the number, about 18 percent, and the average survival time is about 16 months. Where the initial resistance that occurs in patients with 4 people, about 24% of the number of drug-resistant group(about 4% of the total number of patients), 13 patients with secondary resistance, or about 76% of the number of drug-resistant group(about patients 14% of the total); 78 non-resistant patients, with an average survival time of about 28 months. After a long time of both overall survival test P <0.05, the difference was statistically significant. Generation and age-resistant(P = 0.318), gender(P = 0.075) were not statistically significant, due to less number of cases pathology section, temporarily unable to do statistical analysis.Conclusions:1.experiment:Resistant cells measured IC50 value of about 0.289,sensitive cells IC50 value of about 0.009,multiple drug resistance of about 32.11,Resistant cell lines were cultured successfully。2. The survival time has significant differences between the patients who resistant to drugs and the patients who do not resistant to drugs.3. Drug causes the patient’s age, gender, symptoms, tumor size, stage of disease, histological type were not related, needs to be further explored...