| Objective: Octreotide (OCT) has been generally accepted as a tumor growthinhibitor, and has the advantage of little side effect, but its half-time is too short. Inorder to make up to this shortcoming, we added plolxamer407(P407) to OCT to getdelayed-releasing OCT-poloxamer407thermosensitive gel(OCT-P407). In previouscell experiments, we had confirmed that the delayed-releasing preparation of OCT-P407could suppress the proliferation and induce the apoptosis of Hca-F liver cancer cells inmice. And it has been proved in vivo experiments that OCT-P407haddelayed-releasing effect. In this article, we studied the influence of OCT-P407on theproliferation and apoptosis of Hca-F liver cancer cells in the transplantation tumor micemodel. And we aimed to find a new preparation of intratumor injection for the patientsat the end stage of hepatic carcinoma.Methods：After collecting the second generation ascites liver cancer cells andadjusting the cell concentration, the mouse was vaccinated subcutaneously with thiskind of cell suspension in the left armpit to build the mice model of transplantationtumor of Hca-F cells. The mice were divided into five groups (n=10). OCT-P407,dehydrated alcohol, OCT solution, P407solution and normal saline (NS) were injectedinto tumor cavities respectively under the guidance of ultrasound in different group. At0、2、4、6and8days after administration, we measured tumor sizes, and calculatedtumor volumes, weights and inhibition rates separately. Moreover,immunohistochemistry method was used to detect the protein expression levels ofsomatostatin receptors-2(SSTR-2), vascular endothelial growth factor(VEGF) andcysteinyl aspartate specific proteinase-3(Caspase-3), and RT-PCR was used to detect the mRNA expression levels of SSTR-2, VEGF and Caspase-3.Results1. Tumor volume change: The tumor volumes of OCT-P407group decreasedsignificantly at4,6and8days after administration when compared with those of OCTsolution group (P <0.05). And the tumor volumes of OCT-P407group decreasedsignificantly at2,4,6and8days after administration when compared with those of NSgroup and P407group (P <0.05).2. Tumor weight and inhibition rate:8days after the treatment, tumor bodies wereseparated and it was found that the tumor volumes of NS group and P407group werethe largest, followed by those of OCT solution group, and the tumor volumes ofdehydrated alcohol and OCT solution group were the smallest. The comparisons oftumor weights (g) showed that both the tumor weights of OCT-P407group (1.43±0.07)and dehydrated alcohol group (1.32±0.1) were lighter than those of OCT solution group(3.31±0.13), NS group (4.27±0.38) and P407group (3.14±0.07)(P<0.05). Whenconsidering inhibition rates, the index of OCT-P407group was lower than that ofdehydrated alcohol group (P<0.05), while it was higher than those of OCT solutiongroup, NS group and P407group.(P<0.05).3. SSTR-2, VEGF, Caspase-3protein expressions and significances:(1) SSTR-2expression: the number of SSTR-2positive cells with yellow dyeing cytoplasmicgranules, dyeing intensity and positive areas of OCT-P407group increased comparedwith the OCT solution group (P <0.05), and the indexes mentioned above were moresignificant when comparing to those of P407and NS group (P<0.05).(2) VEGFexpression: the number of VEGF positive cells with yellow dyeing cytoplasmicgranules, dyeing intensity and positive areas of OCT-P407group reduced whencompared with those of OCT solution group(P<0.05), and the indexes were moresignificant when comparing to those of P407and NS group (P<0.05).(3) Caspase-3expression: the number of Caspase-3positive cells with yellow dyeing cytoplasmicgranules, dyeing intensity and positive areas of OCT-P407group increased whencomparing to those of OCT solution group(P<0.05), and the indexes were moresignificant when comparing to those of P407and NS group(P<0.05).4. SSTR-2, VEGF, Caspase-3mRNA expressions and significances:(1) SSTR-2mRNA expression: the expression in OCT-P407group increased than that in OCTsolution group (P <0.05), and the increment was more significant when comparing tothose of P407and NS group (P<0.05).(2) VEGF mRNA expression: the expression in OCT-P407group reduced when compared with dehydrated alcohol group(P<0.05), andthe reduction was more significant when comparing to that of OCT solution group(P<0.05), and the expression reduced the most when compared with P407and NSgroup(P<0.05).(3) Caspase-3mRNA expression: the expression in OCT-P407groupincreased than that in OCT solution group (P<0.05), and the increment was mostsignificant when comparing to those of NS and P407group.(P<0.05).Conclusions：1. Intratumor injected OCT-P407can restrain the growth of the Hca-F liver cancersubcutaneous transplantation tumor in mice when comparing to OCT solution, and theeffect becomes more obvious with the extension of time.2. OCT-P407is more effective than OCT solution when considering thesuppression of SSTR-2combination, inhibition of angiogenesis and inducing cellapoptosis.3. The function of OCT-P407is closed to that of dehydrated alcohol in a certainrange. |
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