Discordant influence of amphotericin B on epirubicin cytotoxicity in primary hepatic malignant cells collected by a new primary culture technique.
BACKGROUND
The purpose of this prospective study was to investigate whether amphotericin B (AmB) had any potential role in the systemic chemotherapy of primary hepatic malignancy using cancer cells collected by the authors' method of primary culture.


METHODS
The specimens obtained by ultrasound-guided fine-needle aspiration biopsy (22 G) from 15 patients with hepatocellular carcinoma (HCC) and one with cholangiocarcinoma were plated into culture flask without disaggregation by trypsin-ethylenediamine tetra-acetic acid solution. Six patients with HCC and one patient with cholangiocarcinoma (7/16, 44%) had successful culture and the cancer cells at the 4th passage were continuously exposed to therapeutic ranges of epirubicin (0, 0.5, 1.0, 1.5, 2.0 microg/mL) with or without the combination of 2.5 microg/mL AmB for 24 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to evaluate the effects of the drugs. A human HCC cell line (HA 22T/VGH) was studied for comparison.


RESULTS
Addition of AmB showed no influence on epirubicin cytotoxicity in two patients (one partial resistant HCC and one epirubicin-sensitive cholangiocarcinoma; 25%), augmentation of the epirubicin cytotoxicity in two patients (one total resistant HCC, partial resistant HA 22T/VGH cell line and one epirubicin-sensitive HCC; 37.5%), and decrease of epirubicin cytotoxicity in the remaining three (one partial resistant and two epirubicin-sensitive HCC; 37.5%).


CONCLUSIONS
Amphotericin B has a discordant influence on epirubicin cytotoxicity in primary cultured hepatic malignant cells. Application of AmB in the systemic chemotherapy of primary hepatic malignancy should be limited to patients with positive AmB effect evaluated by an in vitro sensitivity test such as the present method.
Lin
Zu-Yau
ZY
Department of Internal Medicine and Neurology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan. linzuyau@yahoo.com
Chuang
Wan-Long
WL
Chuang
Yen-Hwang
YH
Yu
Ming-Lung
ML
Hsieh
Ming-Yuh
MY
Wang
Liang-Yen
LY
Tsai
Jung-Fa
JF
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D044963:Biopsy, Fine-Needle; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000473:pathology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D000666:Amphotericin B