cyclin-d1 and Sarcoma-180

Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth.. We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 μg/kg b.w./day for first five days then next ten days with166 μg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study.. Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery - heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time.. Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned.

Topics: Animals; Ascites; Ascitic Fluid; Benzoquinones; Blood Cell Count; Cell Cycle; Cell Proliferation; Cell Survival; Cyclin D1; Flow Cytometry; HSP90 Heat-Shock Proteins; Lactams, Macrocyclic; Mice; Mitotic Index; Peritoneal Neoplasms; Sarcoma 180; Survival Analysis; Telomerase

To study the anti-tumor activity of Scurrula parasitica polysaccharides (SP). Water extraction and ethanol precipitation were used to isolate SP from S. parasitica leaf. S180, K562 and HL-60 cell lines proliferation inhibition by SP were detected by MTT assay. The expressions of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP+ SP could not inhibit cancer cell proliferation. SP ip could inhibit the growth of sarcoma S180 in mice, 100 mg x kg(-1) x d(-1). SP ip was the optimal dose on inhibiting S180 growth, with the tumor inhibition rate of 54%. The expression of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP. The result showed that SP could down-regulate the expression of Ki-67, CyclinD1 and Bcl-2 protein, and up-regulate the expression of Bax protein. It indicted that inhibiting cancer cell proliferation and promoting cancer cell apoptosis in vivo maybe one of the anti-cancer mechanisms of SP.

Topics: Animals; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Drugs, Chinese Herbal; Female; HL-60 Cells; Humans; Immunohistochemistry; K562 Cells; Loranthaceae; Male; Mice; Plants, Medicinal; Polysaccharides; Proto-Oncogene Proteins c-bcl-2; Sarcoma 180