| Objective:To detect effect of zoledronic acid on gastric cancer SGC-7901 cell line and SGC-7901 / ADR adriamycin resistant cell line proliferation, invasiveness and adhesion, and further study Zoledronic acid whether has added antitumor effect with adriamycin.Methods: The gastric cancer cell line SGC-7901 and SGC-7901 / ADR adriamycin resistant cell line were cultured in vitro, the effects of zoledronic acid and doxorubicin on the two cell lines were measured: The proliferation ability of cell were counted by MTT, and inhibition rate was calculated; cell adhesion ability were determined by MTT method; Transwell experimental determination of cell invasion ability;The Content of MMP-2, sICAM were determined by ELISA method; And Real-Time PCR change investigated the MMP-2, TIMP-2, MMP-9, ICAM - 1, CD44 expression in the cells.Results:①Gastric cell line SGC-7901 and SGC-7901/ADR incubated with zoledronic acid for 48h in different concentration 10-6,10-5,10-4,10-3 mol / L, respectively, the inhibition rates were 4.98% ,12.19%,27.34%,73.13% and 8.30%, 9.50%, 12.50%, 92.1%. Compared with control, the inhibition rate was higher significantly (P <0.01), the inhibition effectiveness were enhanced along with the dose increasing and the time extension (P <0.05).②SGC-7901 and SGC-7901/ADR incubated with Zoledronic acid (Z) 10-4 mol /L and Doxorubicin (A) 0.5μg/ml, respectively, or combination (Z + A) for 2h, 4h, 6h, the adhesion rate of SGC-7901 were: control (C) group 5.03%, 24.38%, 59.65%, Z group 4.40%, 19.77%, 51.22%, A group of 4.28%, 18.62%, 51.02%, Z+A group, 4.02 %, 15.02%, 46.95%; SGC-7901/ADR were: C group 2.97%, 14.80%, 44.32%, Z group 2.34%, 9.63%, 34.73%, A group o2.05%, 9.70%, 33.85%, Z+A group 2.06%, 8.47%, 31.30%. The adhesion rates were reduced after incubated with different medicament concentration (P <0.05).③In the study of cell invasion, The cell numbers per high power lens field were: 105.11±10.43, 98.37±15.75, 96.19±9.24, 83.02±19.72 in SGC-7901 after treated with Z, A or Z+A at different concentration, the resistant cell line SGC-7901/ADR were 103.73±7.84, 47.64±9.62, 63.47±14.42, 21.58±18.57. Compared with control, signal medicament has weak effectiveness in invasiveness in SGC-7901 (P> 0.05), whereas in Z+C group it was significantly decreased (P <0.05). The invasiveness is obviously declined in SGC-7901/ADR either Z, A or Z+A group (P <0.01).④The expression of CD44 mRNA of C, Z, A or Z+A groups was 0.48±0.03, 0.26±0.02, 0.25±0.02, 0.13±0.01 in SGC-7901 after treated with same medicament concentration and method, in SGC-7901/ADR, it was 1.00±0.02, 0.26±0.00, 0.47±0.03, 0.10±0.01,respectively. The expression of ICAM-1 mRNA of C,Z,A or Z+A groups was 0.74±0.05, 0.55±0.04, 0.37±0.03,0.20±0.02 in SGC-7901.In SGC-7901/ADR ,it was 1.00±0.05, 0.89±0.04, 0.66±0.03, 0.15±0.01, respectively. The expression of MMP-2 mRNA of C, Z, A or Z+A groups was 0.77±0.09, 0.59±0.16, 0.74±0.08, 0.46±0.05 in SGC-7901. In SGC-7901/ADR, it was 1.00±0.06, 0.54±0.27, 0.48±0.03, 0.22±0.02, respectively. The expression of MMP-9 mRNA of C, Z, A or Z+A groups was 0.13±0.02, 0.11±0.01, 0.06±0.00, 0.05±0.00 in SGC-7901. In SGC-7901/ADR ,it was 1.00±0.04, 0.20±0.01, 0.39±0.05, 0.13±0.01, respectively. The expression of TIMP-2 mRNA of C, Z, A or Z+A groups was 0.58±0.07,1.15±0.06, 0.88±0.10, 1.42±0.06 in SGC-7901. In SGC-7901/ADR, it was 1.00±0.05, 2.39±0.11, 4.64±0.54, 8.38±1.17, respectively.Conclusion: Zoledronic acid could inhibit gastric cancer cell line SGC-7901 proliferation, reduce cell adhesion and invasion, maybe reverse SGC-7901/ADM resistant doxorubicin, and have co-effectiveness with doxorubicin. These effectiveness may be related with decreased expression of ICAM-1, MMP-2, MMP-9, CD44 mRNA and increased TIMP-2 mRNA transcription. |
PDF Full Text Request