In vitro and in vivo Growth Inhibition of SC-M1 Gastric Cancer Cells by Retinoic Acid

Abstract

Retinoids are differentiating agents that have been used successfully for the treatment of acute promyelocytic leukemia. When combined with interferons, they are active in preventing second malignancies in patients with head and neck cancer. Our previous studies have demonstrated cytostatic effects of all-trans-retinoic acid (tRA) on SC-M1 gastric cancer cells in vitro. The activity of tRA and 13-cis-retinoic acid (cRA) on SC-M1 cells was compared both in vitro and in vivo in this study. Measurement of total cellular DNA was used to determine cell growth in vitro. The effect of retinoic acid on tumor growth was evaluated by implanting sustained release tRA or cRA pellets into athymic nude mice. The results showed that tRA was more potent than cRA in suppressing the growth of SC-M1 gastric cancer cells in vitro. Both tRA and cRA were effective in suppressing the growth of SC-M 1 tumors in athymic nude mice. No change in the differentiation status and cell cycle phase distribution in excised tumors was observed. Side effects such as bone fractures and weight loss were observed in mice of both treatment groups. The results suggest that retinoic acid may provide therapeutic advantages for the treatment of gastric cancer.

Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization

“…Epidemiological and animal studies have demonstrated the activities of retinoids in prevention (Haenszel et al, 1985;Miasoedov et al, 1989) and treatment (Fujii et al, 1991) of gastric cancer. These studies support our recent observation of the growth suppressive activity of all trans RA and 13-cis RA on gastric cancer cells in vitro and in vivo (Shyu et al, 1995;Jiang et al, 1996). To further understand the roles of nuclear retinoid receptors in gastric mucosa, we have used an in situ hybridization method to detect expression of subtypes of RAR and RXR in histological sections of formalin-fixed, paraffinembedded gastric tissues from normal individuals and gastric cancer patients.…”

Bcl-2 accelerates retinoic acid-induced growth arrest and recovery in human gastric cancer cells

“…Growth arrest by RA in most research models is irreversible [20][21][22], this makes the correlation of the biological response with growth regulation or differentiation difficult. However, SC-M1 cells offer a unique system by which RA treatment can induce reversible growth arrest and morphological changes [11][12][13]. Any biological event can be better correlated with RA-induced growth arrest if it appears with RA treatment and disappears after the removal of RA.…”

“…Retinoic acid (RA)-inhibited growth of SC-M1 cells can be maintained for 70 days by continuous RA exposure, and remains reversible after the removal of RA [11][12][13]. This provides an excellent system to study mechanisms involved in growth reguAbbreviations used : DMEM, Dulbecco's modified Eagle's medium ; FBS, fetal-bovine serum ; p21, cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) ; RA, retinoic acid ; m.o.i., multiplicity of infection.…”

Isolation and Characterization of a HpyC1I Restriction-Modification System in Helicobacter pylori

“…Section 1734 solely to indicate this fact. human gastric cancer tissue (15), was used in this study. This cell line was proved to be Le b -negative and sLe x -positive by monoclonal antibodies against Le b (Seikagaku, Tokyo, Japan) and sLe x (Chemicon, Temecula, CA), respectively.…”