Targeting Molecular Pathways with Camptothecin as Novel Therapy for Gastric Cancer

David A. Litvak, Harry T. Papaconstantinou, B. Mark Evers, Courtney Townsend

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Novel chemotherapeutic agents are needed to treat gastric cancer for which the prognosis remains dismal. The antitumor alkaloid camptothecin (CPT) may be useful in the treatment of certain solid tumors; however, its effects on gastric cancer are largely undefined. The purpose of our study was to characterize the effects of CPT on human gastric tumors in vivo and to determine the cellular mechanisms involved in CPT-mediated inhibition. Two human gastric cancers, WIL and TOR, were transplanted subcutaneously into athymic nude mice. After tumors reached 50 to 100 mm2, mice were randomized into three groups to receive injections of either low-dose CPT (5 mg/kg), high-dose CPT (10 mg/kg), or vehicle (control) intraperitoneally 3 days a week for 3 weeks. Tumors were measured and weighed, and protein levels of the cell cycle inhibitor, p21Wafl/CiPl, and the antiapoptotic protein, Bcl-2, were assessed. Both dosages of CPT significantly inhibited growth of WIL and TOR gastric tumors. CPT (10 mg/kg) reduced tumor size compared to baseline, establishing this as a tumoricidal dosage. Treatment with CPT was associated with increased levels of p21Walf/CiPl and decreased levels of Bcl-2. CPT effectively kills human gastric cancers associated with increased levels of p21Wafl/Cipl and decreased levels of Bcl-2. By activating cell cycle withdrawal and cell death through induction of p21Wafl/Cipl and downregulation of Bcl-2, CPT may be an effective agent for gastric cancer. (J GASTROINTEST SURG 1999;3:618-624.).

Original languageEnglish (US)
Pages (from-to)618-624
Number of pages7
JournalJournal of Gastrointestinal Surgery
Volume3
Issue number6
StatePublished - Nov 1999

Fingerprint

Camptothecin
Stomach Neoplasms
Therapeutics
Neoplasms
Nude Mice
Stomach
Cell Cycle Proteins
Alkaloids
Cell Cycle
Cell Death
Down-Regulation

Keywords

  • Apoptosis
  • Bcl-2
  • Camptothecin
  • Cell cycle
  • Gastric cancer

ASJC Scopus subject areas

  • Surgery

Cite this

Targeting Molecular Pathways with Camptothecin as Novel Therapy for Gastric Cancer. / Litvak, David A.; Papaconstantinou, Harry T.; Evers, B. Mark; Townsend, Courtney.

In: Journal of Gastrointestinal Surgery, Vol. 3, No. 6, 11.1999, p. 618-624.

Research output: Contribution to journalArticle

Litvak, David A. ; Papaconstantinou, Harry T. ; Evers, B. Mark ; Townsend, Courtney. / Targeting Molecular Pathways with Camptothecin as Novel Therapy for Gastric Cancer. In: Journal of Gastrointestinal Surgery. 1999 ; Vol. 3, No. 6. pp. 618-624.
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