Bcl-2 expression correlates with apoptosis induction but not tumor growth delay in transplantable murine lymphomas treated with different chemotherapy drugs

Michael D. Story, Nena Mirkovic, Nancy Hunter, Raymond E. Meyn

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Purpose: Previously, we have reported that the bcl-2-expressing murine lymphoma cell line LY-ar is resistant to chemotherapy-induced apoptosis when compared to the non-bcl-2-expressing LY-as cell line. The intent of the present study was to determine whether this relationship extends to lymphomas produced from these cell lines in syngeneic mice, after treatment with the same chemotherapy agents. Methods: LY-ar and LY-as tumors were grown in the hind legs of syngeneic mice. They were subsequently exposed to graded doses of cisplatin (CP), etoposide (VP-16), Adriamycin (ADR), cytarabine (ara-C), cyclophosphamide (CY), or camptothecin (CAM). Apoptotic bodies were scored in histological sections of tumors that had been stained with hematoxylin and eosin. Tumor growth delay was determined on tumors that were treated when they were 8 mm in diameter. Thereafter, tumor diameter was measured daily with a vernier caliper until they had grown to a maximum of 16 mm in diameter. Results: When transplanted into host animals, tumors derived from these two cell lines and treated in vivo with CP, VP-16, ADR, ara-C, CY, and CAM displayed apoptotic propensities similar to those seen in the same cell lines when treated in vitro. Generally, for all the drugs tested, apoptotic indices in LY-as tumors were significantly higher than in LY-ar tumors. However, tumor growth delay measurements could not be predicted with any accuracy from the apoptotic indices. For some drugs LY-ar tumors were more sensitive than LY-as tumors (CP, Vp-16, ADR, ara-C), yet LY-ar tumors were more resistant to CY. Conclusions: Despite considerable interest in using apoptotic indices as predictors of treatment outcome, the data presented here suggest that these relationships are very complex. This may be especially true for chemotherapy agents for which effects in vivo are complicated by pharmacokinetics, host effects, and tumor cell heterogeneity.

Original languageEnglish (US)
Pages (from-to)367-371
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume44
Issue number5
DOIs
StatePublished - Oct 7 1999

Keywords

  • Adriamycin
  • Apoptosis
  • Camptothecin
  • Cisplatin
  • Cyclophosphamide
  • Cytarabine
  • Etoposide
  • Tumor growth delay

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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