Synergistic effect of SNDX-275 with lapatinib or erlotinib in breast, lung, or head and neck cancer cell lines expressing HER- 2

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14566-e14566
Author(s):  
S. E. Witta ◽  
V. Franekova ◽  
K. Yoshida ◽  
I. Igolnikov ◽  
B. Frederick ◽  
...  

e14566 Background: We previously demonstrated the synergistic effect of the histone deacetylase inhibitor SNDX-275 and gefitinib in non-small cell lung cancer (NSCLC) cell lines lacking E-cadherin expression. We evaluated the combination effect of SNDX- 275 with erlotinib or lapatinib in lung, head and neck (H&N) and breast cancer cell lines resistant to erlotinib or lapatinib(IC50> 1uM) and expressing Her2. Methods: This study included 10 H&N and 17 NSCLC cell lines, 2 breast cancer cell lines with expressing Her2 (SK BR3, MCF7) and one lacking Her2 expression, MDA-MB231. Cell lines were incubated for 5 days with increasing concentrations (0.16, 1 and 6μM) of SNDX-275, lapatinib and erlotinib alone or in combination. The growth inhibitory effect was analyzed with MTT assay. The combination drug effect was evaluated using CalcuSyn (Cambridge, UK). E-cadherin and Her2 expression was evaluated using microarray analysis and RT-PCR. Her2 was considered positive if the relative expression was >300 by RT-PCR. Protein expression was analyzed with western blots. Results: Among the 17 NSCLC and 10 H&N cell lines 16 (12 NSCLC and 4 H&N) had positive Her2 RNA expression. 2 NSCLC (A549, H1703) and 2 H&N (UMSCC10, UMSCC19) were resistant to erlotinib or lapatinib (IC50>1μM). The 2 breast cancer cell lines 2, MCF7 and MDA-MB-321, were resistant to erlotinib and lapatinib. SNDX-275 increased the expression of E-cadherin in 5 of the 6 cell lines selected (A549, H1703, UMSCC19, MCF7 and MDA- MB-321). Synergistic effect of SNDX-275 1μM and lapatinib 1μM was detected in the MCF7, UMSCC10, UMSCC19 cell lines (Combination Index, CI: 0.09, 0.9, 0.67; respectively), while SNDX-275 1μM and erlotinib 1μM were synergistic in MCF7, MDA-MB-321, H1703 and A549 (CI: 0.2, 0.95, 0.58, 0.32; respectively). Conclusions: The combination of SNDX-275 and erlotinib or lapatinib is active in breast, NSCLC, H&N cell lines resistant to either drug alone. [Table: see text]

2021 ◽  
pp. 002215542110552
Author(s):  
Chidalu A. Edechi ◽  
Maryam Amini ◽  
Mohammad K. Hamedani ◽  
Lucas E.L. Terceiro ◽  
Barbara E. Nickel ◽  
...  

The tight junction membrane protein claudin 1 and the adherens junction protein E-cadherin play critical roles in cell–cell communication and in cell signaling. As a result, their protein levels and distribution in cancer have been a focus of cancer researchers in recent years. The loss of sensitivity to contact inhibition and the establishment of invasive properties in cancer are thought to be a result of the mislocalization of these membrane proteins to the cytoplasm. However, reports on their distribution and levels have been inconsistent. It is therefore critical that the techniques used to determine the cellular localization of these proteins be both consistent and reliable. This study was undertaken to determine the optimal fixation method, methanol or formalin, for the detection of claudin 1 and E-cadherin by immunofluorescence in five different human breast cancer cell lines. Both methods exhibited staining of the cell membrane and cytoplasm, but the strongest and most distinct signals were obtained using methanol fixation. Interestingly, cell-specific differences were also observed that appeared to be associated with levels of claudin 1 and E-cadherin as seen by Western blotting. Therefore, when evaluating cellular localization of the junction proteins claudin 1 and E-cadherin, expression level and cell type differences must be considered:


2015 ◽  
Vol 18 (4) ◽  
pp. 329 ◽  
Author(s):  
Sonia Ávila-Arroyo ◽  
Gema Santamaría Nuñez ◽  
Luis Francisco García-Fernández ◽  
Carlos M. Galmarini

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 348 ◽  
Author(s):  
Julie Lafontaine ◽  
Jean-Sébastien Boisvert ◽  
Audrey Glory ◽  
Sylvain Coulombe ◽  
Philip Wong

Cancer therapy has evolved to a more targeted approach and often involves drug combinations to achieve better response rates. Non-thermal plasma (NTP), a technology rapidly expanding its application in the medical field, is a near room temperature ionized gas capable of producing reactive species, and can induce cancer cell death both in vitro and in vivo. Here, we used proliferation assay to characterize the plasma sensitivity of fourteen breast cancer cell lines. These assays showed that all tested cell lines were sensitive to NTP. In addition, a good correlation was found comparing cell sensitivity to NTP and radiation therapy (RT), where cells that were sensitive to RT were also sensitive to plasma. Moreover, in some breast cancer cell lines, NTP and RT have a synergistic effect. Adding a dose of PARP-inhibitor olaparib to NTP treatment always increases the efficacy of the treatment. Olaparib also exhibits a synergistic effect with NTP, especially in triple negative breast cancer cells. Results presented here help elucidate the position of plasma use as a potential breast cancer treatment.


BIOS ◽  
2012 ◽  
Vol 83 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Daniel J. Kelpsch ◽  
Lauren E. Williams ◽  
Amy Du ◽  
Christopher L. Hulstein ◽  
Michael F. Lahey ◽  
...  

2013 ◽  
Vol 42 (4) ◽  
pp. 1263-1270 ◽  
Author(s):  
TONI IBRAHIM ◽  
CHIARA LIVERANI ◽  
LAURA MERCATALI ◽  
EMANUELE SACANNA ◽  
MICHELE ZANONI ◽  
...  

Author(s):  
Shan-Zhong Yang ◽  
Nobuoki Kohno ◽  
Akihito Yokoyama ◽  
Keiichi Kondo ◽  
Hironobu Hamada ◽  
...  

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