140P - Effects of Sinomenine, Cepharanthine, and Tetrandrine on 2D and 3D Cultured Triple Negative Breast Cancer Cells. (140P)

Date 18 November 2017
Event ESMO Asia 2017 Congress
Session Poster lunch
Topics Drug Development
Basic Science
Presenter Anna Kiyomi
Citation Annals of Oncology (2017) 28 (suppl_10): x39-x41. 10.1093/annonc/mdx658
Authors A. Kiyomi1, R. Miyakawa1, N. Uematsu2, H. Ono2, Y. Nakajima1, T. Hirano2, M. Sugiura1
  • 1Drug Safety & Risk Management, Tokyo University of Pharmacy & Life Sciences, 1920392 - Tokyo/JP
  • 2Clinical Pharmacology, Tokyo University of Pharmacy & Life Sciences, 1920392 - Tokyo/JP

Abstract

Background

P-glycoprotein (P-gp) is known to contribute to chemotherapy resistance. Tetrandrine (TET) has been reported to inhibit P-gp function. Sinomenine (SIN) may have a similar efficacy, while its effect on P-gp have little been clarified. Cepharanthine (CEP), a structural TET analog, has little been investigated for its anti-cancer efficacy. 3-Dimensionally (3D) cultured spheroids reflect in vivo environment closer than 2-dimensionally (2D) cultured cells. Then, we aimed to investigate the suppressive efficacy of these herbal ingredients on the growth of 2D and 3D cultured triple negative breast cancer cells.

Methods

MDA-MB-231 cells were cultured in a well of normal flat bottom plate or DSeA-3D Plate filled with TGP. After incubating in 5% CO2 for one night, cells or spheroids were treated by alone/combination of doxorubicin (DOX), docetaxel (DOC), SIN, CEP, or TET and then further cultured for 48 or 72hs. After incubating, the cell viability in each well was evaluated by WST-8 assay. Likewise, cells or spheroids were treated by DOC and/or a P-gp inhibitor verapamil (Vera) and evaluated the cell viability.

Results

DOX or DOC alone suppressed 2D cultured MDA-MB-231 cells dose-dependently, and significant effects were observed by > 5 × 10−7M DOX or > 2 × 10−8M DOC (p 

Conclusions

3D cultured TNBC cells showed chemotherapy resistance compared with 2D cultured cells, and it may not be because of P-gp. TET, SIN and CEP suppress the 2D cultured TNBC cells, and thus further studies are encouraging for their combined use with anti-cancer drugs.

Legal entity responsible for the study

Tokyo University of Pharmacy & Life Sciences

Clinical trial identification

Legal entity responsible for the study

Tokyo University of Pharmacy & Life Sciences

Funding

None

Disclosure

All authors have declared no conflicts of interest.