The Research On Anti-tumor Activity Of Novel Naphthalimide-derivant SLP9 And SLP11

Objective:In this study, the anti-tumor effects of SLP9 and SLP11, novel naphthalimide-derivant were investigated in vivo and in vitro. we also tested the anti-tumor mechanism of SLP9 and SLP11, which provided the experimental basis and theoretical reference for the further research of the novel naphthalimide-derivant Methods:The anti-perliferative effects of SLP9 and SLP11 in HepG2 cells, SMMC-7721 cells, HCT-16 cells, HT-29 cells, MCF-7 cells and MDA-MB-231 cells were assessed by MTT assay. Apoptotic morphology were observed by HCS with AO/EB staining and apoptotic rate were measured by Annexin V/PI staining. Western Blot was used to dectect the protein expression of PARP-1, Caspase-3, Bcl-2 and Bax in HepG2 cells, SMMC-7721 cells and HCT-116 cells after treatment with different does of SLP9 and SLP11 for 48 hours. We explored SLP9 and SLP11 anti-tumor effects in vivo by H22 solid tumor model in Kun Ming mice, H22 lung metastasis model and CT-26 lung metastasis model in BALB/c mice. Results:1.MTT assay demonstrated that SLP9 exerted an excellent anti-proliferative effects in a dose- and time-dependent manner in HepG2 cells, SMMC-7721 cells, HCT-116 cells, HT-29 cells, MCF-7 cells and MDA-MB-231 cells. The IC50(48h) is(5.49±0.24) ?M,(3.05±0.62) ?M,(7.25±0.84) ?M,(10.40±0.78) ?M,(17.53±1.06) ?M,(11.46±0.96) ?M, respectively.MTT assay demonstrated that SLP11 exerted an excellent anti-proliferative effects in a dose- and time-dependent manner in HepG2 cells, SMMC-7721 cells, HCT-116 cells, HT-29 cells, MCF-7 cells and MDA-MB-231 cells. The IC50(48h) is(6.55±0.48) ?M, and(4.20±0.66) ?M, and(7.28±0.43) ?M, and(18.08±1.24) ?M,(12.52±1.11) ?M,(11.05±0.64) ?M, respectively.2.After treatment with SLP9, we found that the cancer cells apoptosis in a dose-and time- dependent manner. High concentrations of SLP9 treated HepG2 cells, SMMC-7721 cells and HCT-116 cells for 48 h while the percentage of apoptosis were(39.21±11.83)%,(64.83±7.39)%,(49.50±4.72)%. AO/EB staining assay also further confirmed that SLP9 induced HepG2 cells, SMMC-7721 cells and HCT-116 cells apoptosis.After treatment with SLP11, we found that the cancer cells apoptosis in a dose-and time- dependent manner. High concentrations of SLP11 treated Hep G2 cells, SMMC-7721 cells and HCT-116 cells for 48 h while the percentage of apoptosis were(35.06±3.48)%,(41.21±2.83)%,(36.35±12.57)%. AO/EB staining assay also further confirmed that SLP11 induced Hep G2 cells, SMMC-7721 cells and HCT-116 cells apoptosis.3.SLP9 induced cell apoptosis via PARP-1 and Caspase-3 activation and the Bcl-2 famliy was also involved in this apoptosis.SLP11 induced cell apoptosis via PARP-1 and Caspase-3 activation and the Bcl-2 famliy was also involved in this apoptosis.4.We found that SLP9 and SLP11 were highly anti-tumor active against H22 solid tumor growth in KunMing mice and the inhibition rate was 52.63% and 49.47%. Furthermore, SLP9 and SLP11 also interrupted lung metastasis of H22 and CT-26 in BALB/c mice and the inhibition rate was 76.70% and 58.25%, 86.71% and 62.03% respectively. Conclusions:1.SLP9 and SLP11 exerted potentgn anti-tumor activity in vitro and in vivo.2.SLP9 and SLP11 induced cancer cell apoptosis through PARP-1 and Caspase-3 activation.