and -16, were established. They originated from either primary pancreatic cancer biopsy or liver metastasis biopsy, or xenografts of these biopsy specimens in athymic nude mice. The primary tumors were all well differentiated adenocarcinoma of pancreatic duct origin. The six established PK cell lines were all CEA positive and had tumorigenicity in athymic nude mice. Morphology of the xenografted tumors was closely similar to that of the original tumor. PK cells grew slowly with the doubling time of 41.3 to 82 hr and showed aneuploid chromosome pattern. High levels of glucose-6-phosphate dehydrogenase (G6PDH) and lactic dehydrogenase (LDH) were found in each cell extract. Trypsin was not detected in cell extracts except PK-8 and PK-9. In chemosensitivity test, all of PK cell lines were sensitive to aclacinomycin A (ACM), and PK-1 and PK-8 were sensitive to 5-Fluorouracil (5-Fu) at concentrations of 0.02 pg/ml, ACM and l;ug/ml, 5-Fu, when the drugs were used for over 48 hr. At higher concentrations, they showed time independent sensitivity to mitomycin C (MMC). PK-9 was resistant to 5-Fu and MMC. pancreatic cancer cell lines ; xenografted tumors ; chemosensitivity testIn spite of recent advances of diagnostic techniques, it is still difficult to diagnose pancreatic cancer in its early stage. Many chemotherapeutic and radiotherapeutic trials have been tested, but no good results have been obtained yet (Zimmerman et al.

Sensitivities to anti-tumor drugs, mytomycin C (MMC), aclarubicin hydrochloride (ACR), doxorubicin hydrochloride (ADR), cisplatin, and 5-fluorouracil(5FU), were examined using PK-1, -8, -9, -12, -14, and -16 cell lines derived from human pancreatic cancer. These cell lines showed different sensitivities to each of the above anti-tumor drugs. The concentrations required for 50% growth-inhibition (ICJ after 2 hours of exposure were 0.096 to 0.35 pg/ml for MMC, 0.0074 to 0.0076 pg/ml for ACR, 0.033 to 0.23 pg/ml for ADR, 0.35 to 1.9 pg/ml for cisplatin, and 21 to 42 fig/ml for 5FU. IC,, of each anti-tumor drug decreased significantly after 48 hours of exposure. The combination of any two out of MMC, ACR, and 5FU showed synergistic inhibition of the growth of PK-1 and PK-8 cell lines. These results show that MMC, ACR, ADR, cisplatin, and 5FU have sufficient anti-tumor effect against six human pancreatic cancer cell lines even at clinically achievable concentrations and exposure times, and chemotherapy for pancreatic cancers requires naturally effective drug delivery into cancer tissues. Cancer 66:2369-2374,1990. ANCREATIC CANCERS ARE highly resistant to cancer P chemotherapeutic drugs, hence clinical achievement in this field has been unsatisfactory so far. To conduct effective chemotherapy against pancreatic cancers, responsiveness of human pancreatic cancer cells to antitumor drugs must be characterized. Establishment of human pancreatic cancers has been rarely reported,'-6 so that the growth inhibitory effect of anti-tumor drugs on cultured cells has not been extensively investigated. In this study, in an attempt to establish an effective chemotherapeutic regimen against pancreatic cancers, we investigated in vitro susceptibility of human pancreatic cancer cell lines to anti-tumor drugs, effects of time of exposure to agents on cell growth, and drug interactions in combination chemotherapy. Materials and Methods Cell Lines of Human Pancreatic CancersSix long-term cultured cell lines (PK-1, -8, -9, -12, -14, and -16) were established from fresh surgical specimens From the First

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