ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of a proliferation-inducing ligand (APRlL) on colorectal cancer (CRC) cell growth and migration, and to observe the role of APRIL in CRC biological behavior.</p><p><b>METHODS</b>The siRNA plasmid vector targeting APRIL gene (APRIL-siRNA) was transfected into human colorectal cancer SW480 cells and recombinant human APRIL (rhAPRIL) was used to stimulate human colorectal cancer HCT-116 cells. Cell proliferation activity was analyzed using cell counting kit-8 (CCK-8), cell cycle was detected by flow cytometry, and the protein expression of cyclin D1, p21 and Bcl-2 was detected by Western blot analysis. Tumor cell migration and invasion were measured by Transwell chambers. RT-PCR was applied to examine the mRNA expression level of MMP-2 and MMP-9. APRIL-siRNA was used to transfect directly SW480 cells, which were injected subcutaneously into nude mice, then the tumor growth and metastasis were observed.</p><p><b>RESULTS</b>Cell proliferation ability of APRIL-siRNA-transfected SW480 cells was drastically repressed, and the percentage of G0/G1 phase cells was significantly increased (t = 4.12, P < 0.05), accompanied with depressed cyclin D1, Bcl-2 expression and elevated p21 expression. Cell proliferation ability of rhAPRIL-stimulated HCT-116 cells was promoted with a decreased G0/G1 phase ratio (t = 3.31, P < 0.05). cyclin D1 and Bcl-2 protein expression was up-regulated while p21 was down-regulated by rhAPRIL stimulation. Metastatic and invasive capacities of APRIL-siRNA-transfected SW480 cells were significantly inhibited compared with their respective controls (both P < 0.05), accompanied with the deregulated MMP-2 and MMP-9 mRNA expression. Metastatic and invasive capacities of rhAPRIL-stimulated HCT-116 cells were promoted with up-regulated MMP-2 and MMP-9 mRNA expression(both P < 0.05). Tumor growth in the group transfected with APRIL-siRNA appeared to be slower than that in the control groups and the expression of MMP-2, MMP-9 in tumor tissues was depressed in the APRIL-siRNA group.</p><p><b>CONCLUSIONS</b>APRIL facilitates tumor growth and metastasis, and is associated with carcinogenesis and prognosis. Our findings suggest that APRIL might be used as a novel target for the intervention and therapy of colorectal cancer.</p>
Subject(s)
Animals , Female , Humans , Mice , Cell Cycle , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colorectal Neoplasms , Metabolism , Pathology , Cyclin D1 , Metabolism , Genetic Vectors , HCT116 Cells , HT29 Cells , Matrix Metalloproteinase 2 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Mice, Nude , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation , Plasmids , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Proto-Oncogene Proteins p21(ras) , Metabolism , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , Transfection , Tumor Burden , Tumor Necrosis Factor Ligand Superfamily Member 13 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of focused ultrasound (FUS) treatment on cervical microenvironment in infertility women with chronic cervicitis.</p><p><b>METHODS</b>A total of 10 women treated in Infertility Clinic of Obstetrics and Gynecology Hospital of College of Medicine of Zhejiang University were assessed. The women aged from 25 to 34 with normal menstrual cycles had moderate or severe cervical erosion. Ultrasound showed they had normal ovulation. The sperms of their husbands had normal motility and number. The FUS they received had a focal depth range of 4 - 6 mm, a resonant frequency of 9 - 11 MHz, and an output power of 3.5 W. The follow-up time was three months. The changes of cervical mucus and the results of postcoital test were evaluated. The clinical effects on cervical erosion and complications were also evaluated.</p><p><b>RESULT</b>In 6 cases of severe cervical erosion, 2 were cured, 2 were improved significantly (more than 50 % reduction of erosion area) and 2 were improved (less than 50 % reduction of erosion area). In 4 cases of moderate cervical erosion, 2 were cured, 2 were improved significantly. After the treatment, the median of cervical mucus score during LH peak were increased from 11 to 13 (Wilcoxon test, P=0.014). Postcoital test showed that the median of highly motile sperm (grade III and grade II) of 5 high-power field were increased from 22 to 52 (Wilcoxon test, P=0.015). Mild side effects without medical intervention included vaginal fluid in all 10 women, vaginal spotting in 2 women. No serious side effects were observed.</p><p><b>CONCLUSION</b>The focused ultrasound therapy can help to improve the cervical microenvironment for infertility women with moderate or severe cervical erosion without serious side effects.</p>