Study Of Drug Screening And Chemosensitizers Of Pancreatic Adenocarcinomas

Objective (1) To study the sensitivity of the primary pancreatic adenocareinomas to chemotherapeutic drugs. (2) To explore the relationship between the P53 gene mutation and the chemosensitivity of pancreatic cancer. (3) To investigate the sensitizing effects of retinoic acid, tamocifen, indometacin, verapamil and octreotide on chemotherapeutic drugs of pancreatic carcinomas. Materials and Methods (1) the drug sensitivity test often chemotherapeutic drugs to pancreatic cancer cells derived from 40 cases of patients with pancreatic cancer was analyzed by MTT colorimetric assay (2) The P53 protein expression of the tissues of pancreatic cancer was detected by ABC immumohistochemical method. (3) The synergistic cytotoxic effect of retinoic acid, tamocifen, indometacin, verapamil ,octreotide and anticancer drugs on both primary pancreatic cancer cells and cell line PANC- 1 was tested. (4) In search for the possible mechanisms , the concentration of doxorubiein in PANC-l cells , cultured either by doxorubin only or by doxorubin combined with retinoic acid, tamocifen, indometacin, verapamil and octreotide, was measured. And the effect of retinoic acid, tamocifen, indometacin, verapamil and octreotide on cell cycle retention and apoptosis induction of doxorubicin treated PANG-i cells was determined Results (l)The average inhibition rate often chemotherapeutic drugs was: methotrexate28.6%, 5-fliorouracil 41.3%, mitocin-C 45.4%, leurocridtine 38.4% , etoposide 37.6%, cisplatin 39.5%, epirubicin 37.0%, bleomycinA5 33.7%, pirarubicin 38.4% and gemcitabine 42.8%, respectivly. There is no significant difference among these drugs. (2) Twenty one eases of pancreatic cancer expressed positive P53 proteins, including 12 cases of P53(+) and 9 cases of P53(++). Among the P53(-)group ,P53(+) group and P53(++) group , the inhibition rate of the antitumor drLlgs of P53(1-) group was highest, that of P53(+? group lowest. (3) ALL the five drugs, retinoic acid, tamoxifen, indometacin, verapamil and octreotide, enhanced the inhibition ability of antitumor drugs to both primary cells and PANG-i cell lines. (4) Retinoic acid, tamoxifen, indometacin and octreotide influenced the cell cycle of doxombicin treated PANG-i cells, reducing the prolifiration index. And these four drugs also increased the proportion of apoptosis cells induced by doxorubicin. (5) Retinoic acid, tamoxifen and verapamil increased the concentration of doxorubicin in PANG-i cells.Conclusion(l) Using bog screening system to gUide clinical individualizationchemotherapy may be a benificial aPproch to improve the result ofchemotheraPy of pancreatic cancer. (2) P53 gene mutation has a bilateralinfiuence on drug sensitivity to pancreatic cancer. (3) Retinoic acid,tamoxifen, indometacin, veraPamil and octreotide are all chemotheraPysensitizers to pancreatic cancer. The mechanisms of drug sensitizinginclude increasing drug accumulation, cell cycle retention, and aPoptosisinduction.