Growth-inhibitory effect of combination chemotherapy for human pancreatic cancer cell lines.
Sensitivities to anti-tumor drugs, mitomycin 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 (IC50) after 2 hours of exposure were 0.096 to 0.35 micrograms/ml for MMC, 0.0074 to 0.0076 micrograms/ml for ACR, 0.033 to 0.23 micrograms/ml for ADR, 0.35 to 1.9 micrograms/ml for cisplatin, and 21 to 42 micrograms/ml for 5FU, IC50 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.
Matsuno
S
S
First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
Hisano
H
H
Kobari
M
M
Akaishi
S
S
D015250:Aclarubicin / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008937:Mitomycins; D016685:Mitomycin; D015250:Aclarubicin; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil