Figure 1.
Human PanNET cell lines are sensitive to BETi. (a–d) Dose-response curves of NET cell lines treated for 72 h with DMSO or CPI203 (a), (+)-JQ1 (b), PFI-1 (c) or (−)-JQ1 (d) in nine-point four-fold dilutions starting at 20 μM. Error bars represent S.E.M., n=3. Inset: the chemical structures of the compounds. (e) Relative cell numbers to day 0 of BON-1 or QGP-1 cells treated with vehicle or CPI203 over a 10-day period. Error bars represent S.E.M., n=3. Population doubling time of each treatment was listed in the table underneath the cell proliferation curve. (f) Cell cycle analysis at 48 h of BON-1 or QGP-1 cells treated with CPI203, (+)-JQ1, PFI-1 or (−)-JQ1 as indicated. (g) to (j) Knockdown of BET protein BRD4 prevented cell proliferation in BON-1 cells. (g) and (h) mRNA levels (g) or protein levels (h) of BET family genes in BON-1 cell line at 48 h after transfection with 25 nM SMARTpool siRNA oligos against NTC, BRD2, BRD3 and BRD4. Error bars represent S.E.M., n=3. (i) Relative cell numbers to NTC of the siRNA transfected BON-1 cells of the above samples at 24 h, 48 h and 72 h. Error bars represent S.E.M., n=3. (j) Cell cycle profiles of the samples in (i). Error bars represent S.E.M., n=3