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Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms.

Abstract：

:Cholesterol metabolism was studied in cells from two established gynecologic cancer cell lines which were maintained in monolayer cultures. The cell lines were derived and established from poorly differentiated epidermoid cervical carcinoma (EC-50) and endometrial adenocarcinoma (AC-258). The specific activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol de novo synthesis, in AC-258 cells (1,700 pmoles x mg-1 microsomal protein x min-1) was three times higher than that found in EC-50 cells (550 pmoles x mg-1 microsomal protein x min-1). However, epidermoid cervical cancer cells (EC-50) metabolized low-density lipoprotein (LDL), the major transport vehicle for cholesterol in plasma, at a very high rate (14,000 ng x mg-1 cell protein x 6 hours). This rate is fifteen times greater than the rate observed in fetal adrenal tissue and fifty times greater than the rate observed in nonneoplastic gynecologic tissue, each in organ culture. Both cancer cells (EC-50 and AC-258) in monolayer culture were shown to have specific receptors for LDL. These cancer cells demonstrate no defect in LDL metabolism, and lysosomal degradation of LDL was blocked by chloroquine. From the results of studies of specific binding of LDL in tissues obtained from nude mice it was demonstrated that membrane fractions prepared from EC-50 cells, after propagation in the mice, contained fifteen to thirty times more specific binding capacity for [125I]iodo-LDL than vital organs of the mouse, such as the liver, heart, lung, kidney, or brain. The results of these studies are suggestive that certain tumor cells might have a higher affinity for LDL than normal tissues and cytotoxic drugs or radionucleotides ligated to the LDL macromolecule may be utilized for the specific delivery of these agents.

journal_name

Am J Obstet Gynecol

journal_title

American journal of obstetrics and gynecology

authors

Gal D,Ohashi M,MacDonald PC,Buchsbaum HJ,Simpson ER

doi

10.1016/0002-9378(81)90952-2

subject

Has Abstract

pub_date

1981-04-15 00:00:00

pages

877-85

issue

eissn

0002-9378

issn

1097-6868

pii

0002-9378(81)90952-2

journal_volume

139

pub_type

杂志文章

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Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms.