Font Size: a A A

The Relationship Between Chemotherapeutics Sensitivity And The Expression Of ZNF139, MRP1and MMP7in Gastric Cancer Cells SGC-7901and SGC-7901/ADR

Posted on:2013-01-27Degree:MasterType:Thesis
Country:ChinaCandidate:Q W LiuFull Text:PDF
GTID:2234330374459243Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: Gastric cancer is one of the most common malignant tumorsin China with a higher morbidity and mortality. The metastasis and the drugresistance are important reasons to the death of patients with gastriccancer, and also are the two difficulties of current treatment. Studies haveshown that there is such relationship among the abnormal expression of zincfinger protein (ZNF) in different tumor cells and the proliferation, drugresistance, infiltration of tumor cells and angiogenesis. For example, zincfinger E-box-binding protein (ZEB) of zinc finger transcription factor canincrease RNA expression of matrix metalloproteinase2(M M P-2), so it wasconsidered closely associated with tumor metastasis. Interfering andsuppressing the expression of zinc finger protein217(ZNF217), RNA canreverse the resistance of breast cancer cells to doxorubicin, which means it isrelated with drug resistance. Our research found early zinc finger protein139(ZNF139) is related with multiple drug resistance of gastric cancer. Thisexperiment will study the expression of ZNF139, MRP1, MMP7in gastriccancer cells SGC7901and mRNA of gastric cancer resistantcells SGC7901/ADR, and also explore their significance for drugresistance and metastasis in gastric cancer. At the same time, we will makeMTT susceptibility test and analyze the relationship betweenchemo-sensitivity and expression of ZNF139, MRP1and MMP7.Methods: Human gastric cancer cell line SGC7901andresistant-adriamycin gastric cancer cell SGC7901/ADR are our studysubjective. Through the application of cell culture, we detected expressionchanges of ZNF139,MRP1,MMP7mRNA with reverse transcriptionpolymerase chain reaction(RT-PCR),and Western blot test was performed to detect the expression changes of ZNF139, MRP1and MMP7protein inSGC-7901and SGC7901/ADR.Using MTT chemosensitivity test, we detectedsensitivity of two kinds of gastric cancer cells, SGC-7901andSGC7901/ADR, on six kinds of chemotherapy drug, ADR,VCR,5-FU, MMC,CDDP, MTX. At last, we analyze the expression of ZNF139, MRP1andMMP7in the gastric cancer cell lines with statistical methods and P <0.05thatmeans it is statistically significant.Results:1The results of ZNF139,MRP1, MMP7mRNA and protein expression inboth SGC-7901/ADR and SGC7901cells1.1ZNF139,MRP1and MMP7mRNA was expressed in both SGC-7901/ADR and SGC7901cells,and there was significant difference between them(all P<0.05).1.2ZNF139,MRP1and MMP7protein was expressed in both SGC-7901/ADR and SGC7901cells,and there was significant difference betweenthem(all P<0.05).2The correlation ZNF139, MRP1, MMP7protein in both SGC7901/ADRand SGC7901cells2.1There was a positive correlation between ZNF139and MRP1(r=0.557P=0.042) in SGC7901cell. There was a positive correlation between MRP1and MMP7(r=0.579P=0.040)in SGC7901cell.2.2There was a positive correlation between ZNF139and MRP1, MMP7(r=0.661P=0.019;r=0.673P=0.016) in SGC7901/ADR cell. There was apositive correlation between MRP1and MMP7(r=0.863P=0.001) inSGC7901/ADR cell.3Relationship between expression of6kinds of chemotherapy andChemosensitivities in both SGC-7901/ADR and SGC7901cells3.1The inhibition rates of SGC7901/ADR cells for ADR were lower thanSGC7901cells(4.08±1.29)%VS(37.02±8.70)%(P<0.05)3.2The inhibition rates of SGC7901/ADR cells for VCR were lower thanSGC7901cells(18.78±3.06)%VS(30.82±5.65)%(P<0.05) 3.3The inhibition rates of SGC7901/ADR cells for MMC were lower thanSGC7901cells(15.37±2.91)%VS(33.11±5.80)%(P<0.05)3.4The inhibition rates of SGC7901/ADR cells for CDDP were lower thanSGC7901cells(17.03±3.93)%VS (31.25±3.95)%(P<0.05)3.5The inhibition rates of SGC7901/ADR cells for MTX were lower thanSGC7901cells(9.67±1.73)%VS(15.59±3.72)%(P<0.05)4The relationship between ZNF139,MRP1, MMP7protein expression andchemosensitivities in both SGC-7901/ADR and SGC7901cells4.1There was a negative correlation between MRP1protein expression andVCR,CDDP,MTX chemosensitivities in SGC7901cell(r=-0.820P=0.004;r=-0.586P=0.0375;r=-0.742P=0.007).There was a negative correlationbetween MRP1protein expression and ADR,VCR,5-FU,MMC,CDDPchemosen-sitivities in SGC7901/ADR cells(r=-0.803P=0.005;r=-0.755P=0.006;r=-0.614P=0.029;r=-0.563P=0.045;r=-0.633P=0.025).4.2There was a negative correlation between ZNF139protein expression andVCR,MMC chemosensitivities in SGC7901cell(r=-0.667P=0.0175;r=-0.861P=0.001). There was a negative correlation between ZNF139proteinexpression and ADR,VCR,5-FU,CDDP chemosensitivities in SGC7901/ADRcells(r=-0.658P=0.019;r=-0.585P=0.038;r=-0.557P=0.47;r=-0.559P=0.046)4.3There was a negative correlation between MMP7protein expression andVCR,5-FU,MMC,MTX chemosensitivities in SGC7901cell (r=-0.665P=0.018;r=-0.681P=0.015;r=-0.788P=0.007;r=-0.651P=0.042). There was anegative correlation between MMP7protein expression and ADR,VCR,MTXchemosensitivities in SGC7901/ADR cells(r=-0.845P=0.002;r=-0.744P=0.007;r=-0.596P=0.034).Conclusions:1ZNF139, MRP1, MMP7were considered closely associated with gastriccancer cells drug resistance.2The gastric cancer MDR maybe increaced tumor cells invasion and metastas.3It was considered that ZNF139was the common ragulation factor betweenMRP1and MMP7,it plays an important role in the carcinogenesis and development of gastric carcinoma.4Stomach cancer cells resistance doxorubicin in SGC7901also generatesresistance to a variety of mechanism, Furthermore, shows that the ZNF139,MRP1, MMP7involved in the stomach multidrug resistance.5ZNF139, MRP1, MMP7was related to the inhibition rate of somechemotherapy drugs, and are different in two kinds of cells.shows thatstomach cancer cells after drug resistance may change way that the drugresistance mechanism, further explained that the ZNF139, MRP1, MMP7involved in the stomach cancer drug-resistant, many link, many factors andmany mechanism are participat in the stomach multidrug resistancecomplicated process.
Keywords/Search Tags:Zinc finger protein139, Gastric cancer, multidrugresistance metastasis, Zinc finger protein
PDF Full Text Request
Related items