PMID- 9384669
OWN - NLM
STAT- MEDLINE
DCOM- 19971208
LR  - 20181201
IS  - 1355-6568 (Print)
IS  - 1355-6568 (Linking)
VI  - 1
IP  - 2
DP  - 1995 Jun
TI  - Modulation of vindesine and doxorubicin resistance in multidrug-resistant pleural 
      mesothelioma cells by tumor necrosis factor-alpha.
PG  - 123-32
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been shown to enhance the 
      cytotoxicity of a variety of antineoplastic agents. To examine whether 
      multidrug-resistant cells are targets of TNF-alpha, and whether TNF-alpha is 
      capable of modulating chemoresistance of these cells, a pleural mesothelioma cell 
      line (PXF1118L) and two multidrug-resistant sublines thereof were used as 
      experimental models. Drug resistance of these cells was due to P-glycoprotein 
      expression, as confirmed by (1) staining with a monoclonal antibody (MRK16) 
      specific for human P-glycoprotein, (2) decreased accumulation of [3H]vinblastine 
      that was reversed by verapamil, and (3) enhanced cytotoxicity of vindesine in the 
      presence of verapamil. Parental and multidrug-resistant cells exhibited little 
      but comparable sensitivity to TNF-alpha alone. Combining TNF-alpha with vindesine 
      or, to a lesser extent, with doxorubicin, but not with cisplatin, resulted in 
      greater cytotoxicity towards multidrug-resistant cells than seen for each 
      compound alone, indicating a synergism. In contrast, TNF-alpha failed to modulate 
      vindesine or doxorubicin cytotoxicity in parental cells. [3H]Vinblastine 
      accumulation was unaffected by TNF-alpha, and chemoresistance was reduced by 
      TNF-alpha also in the presence of verapamil (10 microM), indicating that 
      TNF-alpha was acting in a way different from calcium-channel blockers. Though the 
      molecular mechanism by which TNF-alpha was enhancing vindesine and doxorubicin 
      cytotoxicity remained undefined in this study, the numbers of TNF-alpha binding 
      sites on parental and on multidrug-resistant cells were similar, and 
      P-glycoprotein expression was unmodulated during the entire 48 h incubation 
      period. In conclusion, we show that TNF-alpha increases the cytotoxicity of 
      anticancer drugs in multidrug-resistant tumor cells by a mechanism that differs 
      from most chemosensitizing agents, including verapamil. Further studies will be 
      needed to clarify the mechanism by which TNF-alpha synergizes with anticancer 
      drugs.
FAU - Licht, T
AU  - Licht T
AD  - University of Freiburg, Department of Internal Medicine 1 (Hematology/Oncology), 
      Germany.
FAU - Lubbert, M
AU  - Lubbert M
FAU - Martens, C
AU  - Martens C
FAU - Bross, K J
AU  - Bross KJ
FAU - Fiebig, H H
AU  - Fiebig HH
FAU - Mertelsmann, R
AU  - Mertelsmann R
FAU - Herrmann, F
AU  - Herrmann F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cytokines Mol Ther
JT  - Cytokines and molecular therapy
JID - 9509183
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 80168379AG (Doxorubicin)
RN  - CJ0O37KU29 (Verapamil)
RN  - RSA8KO39WH (Vindesine)
SB  - IM
EIN - Cytokines Cell Mol Ther 1997 Dec;3(4):282-3
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Cell Survival/drug effects
MH  - Doxorubicin/pharmacokinetics/*toxicity
MH  - *Drug Resistance, Multiple
MH  - *Drug Resistance, Neoplasm
MH  - Humans
MH  - *Mesothelioma
MH  - *Pleural Neoplasms
MH  - Recombinant Proteins/pharmacology
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Verapamil/pharmacology
MH  - Vindesine/pharmacokinetics/*toxicity
EDAT- 1995/06/01 00:00
MHDA- 1997/12/31 00:01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1997/12/31 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
PST - ppublish
SO  - Cytokines Mol Ther. 1995 Jun;1(2):123-32.