DOI: 10.5061/dryad.7mp37
title: Data from: An experimental analysis of the molecular effects of trastuzumab (herceptin) and fulvestrant (falsodex), as single agents or in combination, on human HR+/HER2+ breast cancer cell lines and mouse tumor xenografts

description: Purpose: To investigate the effects of trastuzumab (herceptin) and
 fulvestrant (falsodex) either in combination or alone, on downstream cell
 signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell
 lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse
 xenograft tissue. Methods: Cells were cultivated in the presence of
 trastuzumab or fulvestrant or both. Molecular events that resulted in an
 inhibition of cell proliferation and cell cycle progression or in an
 increased rate of apoptosis were studied. The distribution and abundance
 of the proteins p-Akt and p-Erk expressed in these cells in response to
 single agents or combinatorial treatment were also investigated. In
 addition, the effects of trastuzumab and fulvestrant, either as single
 agents or in combination on tumor growth as well as on expression of the
 protein p-MED1 expressed in in vivo mouse xenograft models was also
 examined. Results: Cell proliferation was increasingly inhibited by
 trastuzumab or fulvestrant or both, with a CI&lt;1 and DRI&gt;1 in
 both human cell lines. The rate of apoptosis increased only in the BT-474
 cell line and not in the ZR-75-1 cell line upon treatment with fulvestrant
 and not trastuzumab as a single agent (P&lt;0.05). Interestingly,
 fulvestrant, in combination with trastuzumab, did not significantly alter
 the rate of apoptosis (in comparison with fulvestrant alone), in the
 BT-474 cell line (P&gt;0.05). Cell accumulation in the G1 phase of
 cell cycle was investigated in all treatment groups (P&lt;0.05), and
 the combination of trastuzumab and fulvestrant reversed the effects of
 fulvestrant alone on p-Akt and p-Erk protein expression levels. Using
 ZR-75-1 or BT-474 to generate in vivo tumor xenografts in BALB/c athymic
 mouse models, we showed that a combination of both drugs resulted in a
 stronger inhibition of tumor growth (P&lt;0.05) and a greater decrease
 in the levels of activated MED1 (p-MED1) expressed in tumor issues
 compared with the use of either drug as a single agent. Conclusions: We
 demonstrate that the administration of trastuzumab and fulvestrant in
 combination results in positive synergistic effects on both, ZR-75-1 and
 BT-474 cell lines. This combinatorial approach is likely to reduce
 physiological side effects of both drugs, thus providing a theoretical
 basis for the use of such combination treatment in order to resolve
 HR+/HER2+ triple positive breast cancer that has previously been shown to
 be resistant to endocrine treatment alone.
description: The molecular effects of
 trastuzumab and fulvestrant on human HR+/HER2+ breast cancer cell lines
 and mouse tumor xenograftsThe data file includes
 the raw data of experiments on BT-474 and ZR-75-1 cell lines in vivo and
 in vitro. Results of cell absorbance were obtained by microplate reader.
 Data of cell apoptosis and cell cycle were analyzed by FlowJo 7.6.1
 software. And results of Western blot were observed using Image Lab or got
 in photograph format directly.The Molecular Effects of
 Trastuzumab and Fulvestrant on Human HR+:HER2+ Breast Cancer Cell Lines
 and Mouse Tumor Xenografts.zip