ABSTRACT
Objective To explore the relationship between FOLFOX Chemotherapy and GSTP1,XRCC1 gene polymorphism in patients with colorectal cancer.Methods 60 cases of colorectal cancer treated in Tumor hospital of Hunan Province from January to December 2014 were selected as the research object.Treat patients with modified FOLFOX regimen,determined the GSTP1 ,XRCC1 gene sequence polymorphism,and explored the relationship between the efficacy and the GSTP1 ,XRCC1 gene sequence polymorphism.Results The number of patients with complete remission and partial remission and the num-ber of patients with stable and progress were not related to the gender,age,tumor location,pathological differentiation,TNM staging of patients (χ2=0.222~1.8,P>0.05).Of all cases,the frequencies of GSTP1A/A,A/G and G/G genotype were 68.3%,23.3% and 8.3%,respectively.GSTP1 gene wild-type (A/A)patients were treated with less efficiency than the GSTP1 gene mutation type (A/G+G/G)patients (χ2=4.493,P=0.034).Of all cases,the frequencies of XRCC1 G/G,G/A and A/A genotype were 58.3%,36.7% and 5%,respectively.XRCC1 gene wild type (G/G)patients with effective rate was higher than that of mutant type (G/A+A/A)patients (χ2=4.691,P=0.030).Conclusion The study showed that GSTP1(A/A),XRCC1 (G/G)gene polymorphism may be associated with clinical response to FOLFOX chemotherapy in advanced colorectal cancer.
ABSTRACT
Objective: To observe the effects of 5-aza-2′-deoxycitydine (5-aza CdR) on the proliferation and transcription of tumor suppressor gene GSTP1 and RASSF1A in prostate cancer cell line PC3. Methods: The status of 5′CpG island methylation of RASSF1A and GSTP1 genes in PC3 was analyzed by methylation specific PCR (MSP) before treatment with 5-aza CdR. RASSF1A and GSTP1 mRNA were quantified by real time PCR during the demethylation process by 5-aza-CdR. MTT assay and flow cytometry were used to examine the proliferative activity of PC3 cells before and after 5-aza-CdR treatment. Results: The 5′ CpG island methylation of RASSF1A and GSTP1 genes were detected in human prostate cancer cell line PC3. Compared with control group, RASSF1A and GSTP1 mRNA expression had no significant change 24 h after culture with 5-aza-CdR; their expression was up-regulated 48 h after cultured with 5-aza-CdR, with significant difference found between 5 μmol/L and 10 μmol/L 5-aza-CdR groups. Compared with control group, the expression of RASSF1A and GSTP1 mRNA was significantly increased 72 h after cultured with all concentrations of 5-aza-CdR. MTT assay and cell cycle examination indicated that exposure to 5-aza-CdR for 24 h and 48 h resulted in no obvious growth inhibition and cell cycle change; exposure to 5-aza-CdR for 72 h induced significant growth inhibition (P<0.05) and cell cycle change (P<0.05); and cells were arrested at G0/ G1, phase. Conclusion: The 5′CpG island methylation of RASSF1A and GSTP1 genes is probably responsible for RASSF1A and GSTP1 silencing in PC3 cells. 5-aza-CdR can inhibit the proliferation of PC3 cells, disturb the cell cycle, and elevate transcription of GSTP1 and RASSF1A.
ABSTRACT
Objective To study the clinical significance of the mRNA expression level of a novel gene which encodes a kind of transmembrane prostate protein induced by androgen-PMEPA1, as it may predict the progress of prostate cancer from hormone-dependent to hormone-independent. Methods We used Real-time PCR to detect the mRNA expression of PMEPA1 and GSTP1 in prostate cancer cell lines (LNCaP, PC-3), epithelia cells of benign prostatic hyperplasia and tissues from 33 patients with prostate cancers and 16 cases of prostatic hyperplasia. Results We found the mRNA expression of GSTP1 and PMEPA1 were both down-regulated in prostate cancer cell lines. The mRNA expression of GSTP1 was up-regulated in 6.1% of cases, down-regulated in 81.8%, and showed no difference in 12.1%. While PMEPA1 was highly expressed in 27.3% of cases, lowly expressed in 27.3%, and not differently expressed in 45.4%. Statistical analysis showed that the mRNA expression of GSTP1 was relevant to ages, but had no relationship with PSA, TNM stage, osseous metastasis or tumor differentiation, while the mRNA expression of PMEPA1 was relevant to osseous metastasis and tumor differentiation, but had no relationship with age, PSA or TNM stage. Conclusions PMEPA1 is possibly a useful biomarker, as it can identify patients with unfavourable prognosis, however, this hypothesis needs to be further studied with large samples.