Sensitivity of endometrial cancer cells from primary human tumor samples to new potential anticancer peptide lactaptin

J Cancer Res Ther. Apr-Jun 2015;11(2):345-51. doi: 10.4103/0973-1482.157301.

Abstract

Purpose: Endometrial carcinoma is the most common gynecologic malignancy which is associated with a poor prognosis when diagnosed at an advanced stage; therefore, the discovery of efficacious new drugs is required to reinforce conventional chemotherapy. Short-term cultures of primary cells from endometrial tumors could be used for testing new anticancer therapeutics as well as for the development of personalized cancer therapy strategy. Here, the antitumor effect of a recombinant analogue of lactaptin (RL2), a new potential anticancer molecule, was examined against primary human endometrial cancer cells.

Materials and methods: Primary cell cultures of malignant and normal human endometrium were performed by enzymatic digestion of endometrial tissue from biopsy material. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the messenger ribonucleic acid (mRNA) state of estrogen (ERs) and progesterone (PRs) hormone receptors and aromatase (Cyp 19) in cell cultures. Dynamic monitoring of cell adhesion and proliferation was made using the iCELLigence system (ASEA Biosciences). The sensitivity of cell cultures to conventional anticancer drugs and the lactaptin analog was estimated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry, and the iCELLligence system.

Results: Established short-term primary cultures of endometrial cancer cells were ERα/ERβ/PR-positive and sensitive for RL2. The IC 50 values of doxorubicin and cisplatin were determined for all of the primary cultures designed. KE normal cells displaying low Cyp19 mRNA levels and high ERβ and PR mRNA levels were more resistant to RL2 treatment as well as to cisplatin and doxorubicin.

Conclusions: Our results indicate that the recombinant analog of lactaptin, RL2, exerts cytotoxic effects against primary hormone-dependent endometrial tumor cells in vitro with features of apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Aromatase / metabolism
  • Caseins / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Doxorubicin / pharmacology
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / metabolism
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Female
  • Humans
  • Middle Aged
  • Peptides / pharmacology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Antineoplastic Agents
  • Caseins
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Peptides
  • RNA, Messenger
  • Receptors, Progesterone
  • estrogen receptor alpha, human
  • lactaptin, human
  • Doxorubicin
  • Aromatase
  • Cisplatin