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Inhibition of gastric cancer by camptothecin involves apoptosis and multiple cellular pathways.
Surgery. 1999 Aug; 126(2):223-30.S

Abstract

BACKGROUND

The prognosis for gastric cancer remains dismal; novel agents that target specific molecular pathways are needed as adjuvant therapy. Camptothecin (CPT), on inhibitor of topoisomerase I, is effective in the treatment of certain solid tumors; its effects on gastric cancer are largely undefined. The purpose of this study was to (1) characterize the effects of CPT on the growth of a human gastric cancer and (2) assess potential cellular mechanisms responsible for CPT-mediated growth inhibition.

METHODS

The human gastric cancer SIIA was transplanted subcutaneously into athymic nude mice. After tumors reached approximately 100 mm2, mice were randomized into 3 groups to receive either CPT (5 or 10 mg/kg) or vehicle (control) intraperitoneally 3 days per week for 3 weeks; tumor size was measured biweekly. To assess potential mechanisms of CPT-mediated inhibition, SIIA cells were treated with CPT (20 mumol/L) and cells were counted over a time course; apoptosis was assessed by Hoechst stain and DNA laddering. Expression of p53 (a tumor suppressor), p21Waf1 and p27Kip1 (cell cycle inhibitors), and Bcl-2 and Bcl-XL (antiapoptotic proteins) was determined.

RESULTS

CPT (5 and 10 mg/kg) significantly inhibited tumor growth of SIIA gastric cancers compared with controls. CPT-mediated inhibition of SIIA cell proliferation was associated with an increase in apoptosis. Moreover, CPT treatment resulted in induction of p53, p21Waf1, and p27Kip1 and a decrease in Bcl-2 and Bcl-XL RNA and protein levels.

CONCLUSIONS

Treatment with CPT effectively inhibited the growth of the human gastric cancer SIIA; the mechanism involved was induction of apoptosis mediated by up-regulation of p53, p21Waf1/Cip1, and p27Kip1 and the down-regulation of Bcl-2 and Bcl-XL. Novel agents such as CPT, which target specific molecular pathways, may prove clinically useful in the adjuvant treatment of gastric cancers.

Authors+Show Affiliations

Department of Surgery, University of Texas Medical Branch, Galveston 77555-0533, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10455888

Citation

Litvak, D A., et al. "Inhibition of Gastric Cancer By Camptothecin Involves Apoptosis and Multiple Cellular Pathways." Surgery, vol. 126, no. 2, 1999, pp. 223-30.
Litvak DA, Papaconstantinou HT, Hwang KO, et al. Inhibition of gastric cancer by camptothecin involves apoptosis and multiple cellular pathways. Surgery. 1999;126(2):223-30.
Litvak, D. A., Papaconstantinou, H. T., Hwang, K. O., Kim, M., Evers, B. M., & Townsend, C. M. (1999). Inhibition of gastric cancer by camptothecin involves apoptosis and multiple cellular pathways. Surgery, 126(2), 223-30.
Litvak DA, et al. Inhibition of Gastric Cancer By Camptothecin Involves Apoptosis and Multiple Cellular Pathways. Surgery. 1999;126(2):223-30. PubMed PMID: 10455888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of gastric cancer by camptothecin involves apoptosis and multiple cellular pathways. AU - Litvak,D A, AU - Papaconstantinou,H T, AU - Hwang,K O, AU - Kim,M, AU - Evers,B M, AU - Townsend,C M,Jr PY - 1999/8/24/pubmed PY - 2001/3/28/medline PY - 1999/8/24/entrez SP - 223 EP - 30 JF - Surgery JO - Surgery VL - 126 IS - 2 N2 - BACKGROUND: The prognosis for gastric cancer remains dismal; novel agents that target specific molecular pathways are needed as adjuvant therapy. Camptothecin (CPT), on inhibitor of topoisomerase I, is effective in the treatment of certain solid tumors; its effects on gastric cancer are largely undefined. The purpose of this study was to (1) characterize the effects of CPT on the growth of a human gastric cancer and (2) assess potential cellular mechanisms responsible for CPT-mediated growth inhibition. METHODS: The human gastric cancer SIIA was transplanted subcutaneously into athymic nude mice. After tumors reached approximately 100 mm2, mice were randomized into 3 groups to receive either CPT (5 or 10 mg/kg) or vehicle (control) intraperitoneally 3 days per week for 3 weeks; tumor size was measured biweekly. To assess potential mechanisms of CPT-mediated inhibition, SIIA cells were treated with CPT (20 mumol/L) and cells were counted over a time course; apoptosis was assessed by Hoechst stain and DNA laddering. Expression of p53 (a tumor suppressor), p21Waf1 and p27Kip1 (cell cycle inhibitors), and Bcl-2 and Bcl-XL (antiapoptotic proteins) was determined. RESULTS: CPT (5 and 10 mg/kg) significantly inhibited tumor growth of SIIA gastric cancers compared with controls. CPT-mediated inhibition of SIIA cell proliferation was associated with an increase in apoptosis. Moreover, CPT treatment resulted in induction of p53, p21Waf1, and p27Kip1 and a decrease in Bcl-2 and Bcl-XL RNA and protein levels. CONCLUSIONS: Treatment with CPT effectively inhibited the growth of the human gastric cancer SIIA; the mechanism involved was induction of apoptosis mediated by up-regulation of p53, p21Waf1/Cip1, and p27Kip1 and the down-regulation of Bcl-2 and Bcl-XL. Novel agents such as CPT, which target specific molecular pathways, may prove clinically useful in the adjuvant treatment of gastric cancers. SN - 0039-6060 UR - https://www.unboundmedicine.com/medline/citation/10455888/Inhibition_of_gastric_cancer_by_camptothecin_involves_apoptosis_and_multiple_cellular_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-6060(99)70159-5 DB - PRIME DP - Unbound Medicine ER -