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Objective: To investigate the antitumor activity of the compound HS-4 and the action mechanism. Methods: MTT method was used to test in vitro antitumor activity of the compound HS-4. Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice, and, in vivo antitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system. Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics, using high-throughput sequencing technology. Results: HS-4 was found to have relatively high in-vitro antitumor activity against liver cancer cells, gastric cancer cells, renal cancer cells, lung cancer cells, breast cancer cells and colon cancer cells. The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively, while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L, respectively. It was demonstrated that HS-4 possessed a better therapeutic effect in liver cancer. Conclusions: A new reliable orthotopic xenotransplantation tumor model of liver cancer in nude mice is established. The new compounds HS-4 was found to possess relatively high in vivo and in vitro antitumor activity against liver cancer cells.
ABSTRACT
OBJECTIVE@#To investigate the antitumor activity of the compound HS-4 and the action mechanism.@*METHODS@#MTT method was used to test in vitro antitumor activity of the compound HS-4. Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice, and, in vivo antitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system. Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics, using high-throughput sequencing technology.@*RESULTS@#HS-4 was found to have relatively high in-vitro antitumor activity against liver cancer cells, gastric cancer cells, renal cancer cells, lung cancer cells, breast cancer cells and colon cancer cells. The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively, while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L, respectively. It was demonstrated that HS-4 possessed a better therapeutic effect in liver cancer.@*CONCLUSIONS@#A new reliable orthotopic xenotransplantation tumor model of liver cancer in nude mice is established. The new compounds HS-4 was found to possess relatively high in vivo and in vitro antitumor activity against liver cancer cells.
ABSTRACT
Objective:To investigate the antitumor activity of the compound HS-4 and the action mechanism.Methods:MTT method was used to testin vitroantitumor activity of the compound HS-4. Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice, and,in vivoantitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system. Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics, using high-throughput sequencing technology. Results:HS-4 was found to have relatively highin-vitro antitumor activity against liver cancer cells, gastric cancer cells, renal cancer cells, lung cancer cells, breast cancer cells and colon cancer cells. The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively, while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L, respectively. It was demonstrated that HS- 4 possessed a better therapeutic effect in liver cancer.Conclusions: A new reliable orthotopic xenotransplantation tumor model of liver cancer in nude mice is established. The new compounds HS-4 was found to possess relatively highin vivo andin vitroantitumor activity against liver cancer cells.
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Objective: Methylotropic yeast pichia pastoris system was used to express recombinant human soluble 4 1BBL protein with biological activity. Methods: According to the nuclear acid sequence coding human soluble 4 1BBL, we cloned the genes with PCR from XG 4 1BBL transfection cell line,then the gene fragment for extracellar domain was subcloned into the PUCm T vector and sequence of s4 1BBL cDNA was confirmed by sequencing. The s4 1BBL gene was inserted into the pPICZ?A , which was transformed into Pichia pastoris GS115 by linearized electroportion.The recombinant protein was identified by the assay of SDS PAGE and Western blot. Costimulating activity of rhs4 1BBL on T cell proliferation in vitro was evidenced by 3 H TdR incorporation assay. Results: The s4 1BBL cDNA was successfully obtained and insected into pPICZ?A. The protein molecular weight of hs4 1BBL in the yeast supernamant was about 21 kD by SDS PAGE analyses,and the specificitity was identified by western blot. Finally, rhs4 1BBL protein could costimulate the proliferation of T cells in vitro. Conclusion: The rhs4 1BBL protein was efficiently expressed in Pichia pastoris (GS115)and showed natural biological activities. And it may provide a valuable materials for further study of 4 1BB/4 1BBL.