P-017 - Tanshinone IIA could inhibit gastric carcinoma AGS cells through increasing the protein expression levels of p-p38, TNF-α, Bax and CHOP but decreas...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Basic Science
Gastric Cancer
Presenter C.C. Su
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors C.C. Su
  • Changhua Christian Hospital, Changhua/TW

Abstract

Introduction

Tanshinone IIA (Tan-IIA; C19H18O3), a phenanthrenequinone derivative extracted from Salviae Miltiorrhizae Radix (Danshen), is a natural anti-cancer agent, possesses anti-tumor activity in a variety of human cancer cells, such as breast cancer, lung cancer, pancreas cancer, hepatic cancer and colon cancer. It was well documented that Tan-IIA can exert powerful inhibitory effects with time- and dose-dependent and induce apoptosis in gastric cancer cells SGC7901 and MKN-45. These reports suggest that Tanshinone IIA may serve as an effective adjunctive reagent in the treatment of gastric cancer. However, the molecular mechanisms of Tan-IIA in gastric cancer cells have not been established. Our previous study showed that Tan-IIA inhibits the growth of human gastric cancer AGS cells in vitro. The molecular mechanisms may be through inducing the activation of endoplasmic reticulum stress and MAPK pathway. Tan-IIA also could inhibit human gastric cancer AGS cells through both extrinsic and intrinsic pathway to induce apoptosis.

Methods

In the present study, we investigated the efficacy and molecular mechanisms of Tan- IIA in human gastric cancer AGS cells in vivo. In the in vivo study, human gastric cancer AGS cells (2x106/0.2 ml) were injected subcutaneously into the flank area of nude SCID mice (n = 60). When the xenograft tumors were more than 0.5 cm in diameter. These mice were randomly divided into four groups. Tan- IIA was dissolved in corn oil and then administered to the mice at concentrations of 10, 30 and 90 mg/kg, QW1, 3, 5 by intraperitoneal injection for 8 weeks. The control group was treated with an equal volume of corn oil. SCID mice were scarified by CO2 inhalation and the xenograft tumors were dissected. Subsequently, the protein expression of p-p38, p-JNK, p-ERK, p53, p21, TNF-α, Fas, Caspase-8, Bip, PDI, Calnexin, Calreticulin, IRE1α, PERK, elF2-α, ATF6, ATF4, Caspase-12, Caspase-9, CHOP, Bax, Mcl-1, TCTP, Bcl-xl and Caspase-3 in the tumors was measured by Western blotting.

Results

The results showed Tan-IIA can inhibit the xenograft tumor with dose dependent. The protein expression levels of p-p38, p-JNK, p53, p21, TNF-α, Fas, Caspase-8, Bip, Caspase-12, CHOP, Bax, Caspase-9 and Caspase-3 were increased, but p-ERK, Mcl-1, TCTP and Bcl-xl were decreased in the xenograft tumors with dose dependent.

Conclusion

These findings indicate Tan-IIA could inhibit gastric carcinoma AGS cells through inducing the activation of endoplasmic reticulum stress and MAPK pathway in vivo. Tan-IIA also could inhibit human gastric cancer AGS cells through both extrinsic and intrinsic pathway to induce apoptosis in vivo. These findings agree the in vitro studies. Tan-IIA can inhibit gastric carcinoma AGS cells through the same molecular mechanisms in vitro and in vivo. The chemotherapeutic potential of Tan-IIA for human gastric cancer warrants further study in the future.