Annals of Oncology

abstracts
Results: Using IHC, we demonstrated that 4F2hc is aberrantly expressed in PDAC and
matched adjacent tissue. However, there was no significant difference in 4F2hc
expression in the different grades and stages. Although Kaplan-Meier survival curves
and Cox analyses did not revealed a significant association between 4F2hc expression
and OS, we observed a trend that suggests an association between absence of 4F2hc
expression and prolonged survival. Additionally, our results showed that 4F2hc+ cells
isolated from fresh tumor tissue co-expressed other known markers of PDAC such as
MUC4 and MUC1.To determine the role of 4F2hc in PDAC, cell behavior between
4F2hc+ cells and 4F2hc low expressing cells was compared. We found that 4F2hc
downregulation significantly inhibited tumorsphere formation and cell proliferation by
arresting cell cycle.
Conclusions: Herein, we demonstrated that 4F2hc is overexpressed in resected tumor
tissue as well as in matched adjacent tissue of patients with pancreatic cancer.
Moreover, our data suggests that 4F2hc expression increases tumorigenesis by
enhancing cell proliferation and promoting anchorage-independent growth in vitro.
Although further studies are needed, our results suggest that 4F2hc might be a novel
therapeutic target of PDAC.
Legal entity responsible for the study: Medical University of Vienna
Funding: Medical University of Vienna
Disclosure: All authors have declared no conflicts of interest.
51P
Marine-derived bioactive compound MB-E5 as a cytotoxic
agent in glioblastoma cell lines
S.Y. Cheng 1 , W-F. Chen 2 , P-J. Sung 3 , Z-H. Wen 4
1 Doctoral Digress Program in Marine Biotechnoogy, National Sun Yat-sen
University, Kaohsiung, Taiwan, 2 Department of Neurosurgery, Chang Gung
Memorial Hospital-Kaohsiung, Kaohsiung, Taiwan, 3 Graduate Institute of Marine
Biology, National Dong Hwa University, Pingtung, Taiwan, 4 Department of Marine
Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung,
Taiwan
Background: Glioblastoma multiforme (GBM) is the most common primary central
nervous system tumor. Even with standard and aggressive treatment strategies the
Annals of Oncology
5-year survival rate is less than 30%. Also, previous results reveal that glutathione
S-transferase M3 (GSTM3) is highly expressed in brain tissue and represents the
predominant activity of GSTs, a group of enzymes that mainly facilitates detoxification,
in the human brain. The compound studied here, ME-E5, is extracted from cultured
Vibrio psychroerythrus, a marine bacterial species.
Methods: In this study, the cytotoxic activity of MB-E5 in U87MG and GBM8401
glioblastoma cell lines were investigated using MTT assay and TUNEL assay. Tumor
sphere assay were performed to determine the impact of MB-E5 on in vitro neuron
cancer stem cell growth. Immunofluorescence assay and western blotting were used to
evaluate the level of autophagy-related proteins and the PI3K/Akt pathway. gstm3 gene
expression levels were measured in TMZ-resistant glioblastoma cell line by
semi-quantitative polymerase chain reaction (PCR).
Results: MTT assays show that MB-E5 exhibits higher cytotoxic activity than
Temozolomide (TMZ), a first-line drug in the treatment of gliomas, in GBM cell lines.
Neurosphere formation is significantly reduced at low MB-E5 levels. TUNEL assay and
western blot analysis show that MB-E5 induces apoptosis and reduces glioblastoma cell
survival rate by inhibiting the PI3K/AKT/mTOR signaling pathway. Also,
immunofluorescence assay and western blotting results indicate that MB-E5 promotes
the expression of autophagy marker LC3-II. Furthermore, MB-E5 demonstrates higher
cytotoxicity against TMZ resistant-GBM8401 cells. The results of semi-quantitative
PCR indicate a decrease in the expression of gstm3 after 3 days of 200 µM TMZ
treatment, but the expression level recovers after 15 days of continuous TMZ treatment
in the survival population of GBM cell lines. Moreover, GSTM3 mRNA expression is
reduced after MB-E5 treatment.
Conclusions: These results suggest that the marine-derived bioactive compound
MB-E5 may be effective as a cancer therapeutic agent in glioblastoma. We also theorize
that MB-E5 may reduce gstm3, which could play a key role in TMZ-resistant
glioblastoma cells.
Legal entity responsible for the study: Doctoral Degree Program in Marine
Biotechnology, National Sun Yat-sen University, Taiwan
Funding: Kaohsiung Chang Gung Memorial Hospital and Chang Gung University
College of Medicine, Kaohsiung, Taiwan
Disclosure: All authors have declared no conflicts of interest.
vi14 | abstracts Volume 27 | Supplement 6 | October 2016