PMID- 12110277
OWN - NLM
STAT- MEDLINE
DCOM- 20030314
LR  - 20220311
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 16
IP  - 4
DP  - 2002 Aug
TI  - Role of the lung resistance-related protein (LRP) in the drug sensitivity of 
      cultured tumor cells.
PG  - 389-98
AB  - Drug resistance, one of the major obstacle in the successful anticancer therapy, 
      can be observed at the outset of therapy (intrinsic resistance) or after exposure 
      to the antitumor agent (acquired resistance). To gain a better insight into the 
      mechanisms of intrinsic resistance we have analyzed two human cell types derived 
      from untreated tumors: MCF-7 breast cancer and A549 non small cell lung cancer 
      (NSCLC). We have examined: the cytotoxic effect induced by doxorubicin (DOX); the 
      time course of drug accumulation by flow cytometry and intracellular drug 
      distribution by confocal microscopy; the expression and distribution of proteins 
      related to anthracycline resistance, such as P-gp (P-glycoprotein), MRP1 
      (multidrug resistance-associated protein) and LRP (lung resistance-related 
      protein). The cytotoxicity assays showed that A549 cells were less sensitive than 
      MCF-7 cells to the DOX treatment in agreement with the different DOX uptake. 
      Moreover, while in A549 cells DOX was mostly located in well defined 
      intracytoplasmic vesicles, in MCF-7 cells it was mainly revealed inside the 
      nuclei. The analysis of P-gp and MRP expression did not show significant 
      differences between the two cell lines while a high expression of LRP was 
      detected at the nuclear envelope and cytoplasmic levels in A549 cells. These 
      findings suggest that the lower sensitivity to DOX treatment showed by lung 
      carcinoma cells could be ascribed to drug sequestration by LRP inside the 
      cytoplasmic compartments.
FAU - Meschini, S
AU  - Meschini S
AD  - Laboratory of Ultrastructures, Istituto Superiore di Sanita, Viale Regina Elena 
      299, 00161 Rome, Italy.
FAU - Marra, M
AU  - Marra M
FAU - Calcabrini, A
AU  - Calcabrini A
FAU - Monti, E
AU  - Monti E
FAU - Gariboldi, M
AU  - Gariboldi M
FAU - Dolfini, E
AU  - Dolfini E
FAU - Arancia, G
AU  - Arancia G
LA  - eng
PT  - Journal Article
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Vault Ribonucleoprotein Particles)
RN  - 0 (major vault protein)
RN  - 80168379AG (Doxorubicin)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis
MH  - Antineoplastic Agents/*pharmacology
MH  - Breast Neoplasms/*pathology
MH  - Carcinoma, Non-Small-Cell Lung/*pathology
MH  - Cytoplasm/chemistry
MH  - Doxorubicin/*pharmacology
MH  - Drug Resistance, Neoplasm/*physiology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - *Lung Neoplasms
MH  - Multidrug Resistance-Associated Proteins/biosynthesis
MH  - Neoplasm Proteins/metabolism/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Vault Ribonucleoprotein Particles/metabolism
EDAT- 2002/07/12 10:00
MHDA- 2003/03/15 04:00
CRDT- 2002/07/12 10:00
PHST- 2002/07/12 10:00 [pubmed]
PHST- 2003/03/15 04:00 [medline]
PHST- 2002/07/12 10:00 [entrez]
AID - S0887233302000358 [pii]
AID - 10.1016/s0887-2333(02)00035-8 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2002 Aug;16(4):389-98. doi: 10.1016/s0887-2333(02)00035-8.