Prevention of VP-16 resistance by a disiloxane, SILA409

Effects of SILA409 on the expression of GRP78 in NCI-H446 human small cell lung cancer cells

Encheng Li, Jinhui Zhang, Jiarui Wang, Fei Gao, Zhonghai Yang, Qiang Meng, Qianqian Zhang, Na Li, Ming Huang, G. Spengler, J. Molnár, Qi Wang

Research output: Contribution to journalArticle

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Abstract

Aim: To investigate the effects of an MDR inhibitor and Ca2+ antagonist, the SILA409, on the expression of glucose-regulated protein 78 (GRP78) and the resistance to VP-16 in the NCI-H446 cell line. Methods: Conventional RT-PCR, western blotting and immunofluorescence were used to detect the expression of GRP78 at the mRNA and protein levels in the NCI-H446 cell line treated with varying amounts of SILA409. The viability of cells treated with VP-16 was examined by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and apoptosis was studied via DAPI staining. The Ca2+ ionophore A23187 was used as an upregulator of GRP78. Results: The expression of GRP78 at the mRNA and protein levels in the A23187 Ca2+ ionophore-induced and SILA409-post-treated cells was significantly lower than that in the positive control in the A23187-treated group (p50 values for VP-16 in the SILA409-treated and A23187-pretreated and SILA409-post-treated groups were obviously decreased as compared with the A23187-treated group (33.16±4.91 vs 47.21±8.34, and 33.05±2.97 vs 47.21±8.34, respectively, p2+ ionophore followed by SILA409 treatment was significantly decreased as compared with that of the Ca 2+ ionophore-treated cells. The apoptosis induced by SILA409 treatment, in Ca2+ ionophore-pretreated and SILA409-post-treated cells was significantly increased relative to Ca2+ ionophore-treated cells. An elevated glucose concentration itself does not affect the MDR-reversing effect of SILA409. Conclusion: SILA409 can significantly decrease the overexpression of GRP78 induced by A23187 and increase the sensitivity to VP-16 in the NCI-H446 cell line.

Original languageEnglish
Pages (from-to)691-697
Number of pages7
JournalLetters in Drug Design and Discovery
Volume8
Issue number8
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Ionophores
Small Cell Lung Carcinoma
Calcimycin
Etoposide
Cell Line
Apoptosis
Messenger RNA
Fluorescent Antibody Technique
disiloxane
glucose-regulated proteins
Cell Survival
Proteins
Western Blotting
Staining and Labeling
Glucose
Polymerase Chain Reaction
Therapeutics

Keywords

  • Disiloxane
  • GRP78
  • Multidrug resistance
  • SCLC
  • SILA409
  • VP-16

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Molecular Medicine

Cite this

Prevention of VP-16 resistance by a disiloxane, SILA409 : Effects of SILA409 on the expression of GRP78 in NCI-H446 human small cell lung cancer cells. / Li, Encheng; Zhang, Jinhui; Wang, Jiarui; Gao, Fei; Yang, Zhonghai; Meng, Qiang; Zhang, Qianqian; Li, Na; Huang, Ming; Spengler, G.; Molnár, J.; Wang, Qi.

In: Letters in Drug Design and Discovery, Vol. 8, No. 8, 10.2011, p. 691-697.

Research output: Contribution to journalArticle

Li, Encheng ; Zhang, Jinhui ; Wang, Jiarui ; Gao, Fei ; Yang, Zhonghai ; Meng, Qiang ; Zhang, Qianqian ; Li, Na ; Huang, Ming ; Spengler, G. ; Molnár, J. ; Wang, Qi. / Prevention of VP-16 resistance by a disiloxane, SILA409 : Effects of SILA409 on the expression of GRP78 in NCI-H446 human small cell lung cancer cells. In: Letters in Drug Design and Discovery. 2011 ; Vol. 8, No. 8. pp. 691-697.
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abstract = "Aim: To investigate the effects of an MDR inhibitor and Ca2+ antagonist, the SILA409, on the expression of glucose-regulated protein 78 (GRP78) and the resistance to VP-16 in the NCI-H446 cell line. Methods: Conventional RT-PCR, western blotting and immunofluorescence were used to detect the expression of GRP78 at the mRNA and protein levels in the NCI-H446 cell line treated with varying amounts of SILA409. The viability of cells treated with VP-16 was examined by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and apoptosis was studied via DAPI staining. The Ca2+ ionophore A23187 was used as an upregulator of GRP78. Results: The expression of GRP78 at the mRNA and protein levels in the A23187 Ca2+ ionophore-induced and SILA409-post-treated cells was significantly lower than that in the positive control in the A23187-treated group (p50 values for VP-16 in the SILA409-treated and A23187-pretreated and SILA409-post-treated groups were obviously decreased as compared with the A23187-treated group (33.16±4.91 vs 47.21±8.34, and 33.05±2.97 vs 47.21±8.34, respectively, p2+ ionophore followed by SILA409 treatment was significantly decreased as compared with that of the Ca 2+ ionophore-treated cells. The apoptosis induced by SILA409 treatment, in Ca2+ ionophore-pretreated and SILA409-post-treated cells was significantly increased relative to Ca2+ ionophore-treated cells. An elevated glucose concentration itself does not affect the MDR-reversing effect of SILA409. Conclusion: SILA409 can significantly decrease the overexpression of GRP78 induced by A23187 and increase the sensitivity to VP-16 in the NCI-H446 cell line.",
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T2 - Effects of SILA409 on the expression of GRP78 in NCI-H446 human small cell lung cancer cells

AU - Li, Encheng

AU - Zhang, Jinhui

AU - Wang, Jiarui

AU - Gao, Fei

AU - Yang, Zhonghai

AU - Meng, Qiang

AU - Zhang, Qianqian

AU - Li, Na

AU - Huang, Ming

AU - Spengler, G.

AU - Molnár, J.

AU - Wang, Qi

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N2 - Aim: To investigate the effects of an MDR inhibitor and Ca2+ antagonist, the SILA409, on the expression of glucose-regulated protein 78 (GRP78) and the resistance to VP-16 in the NCI-H446 cell line. Methods: Conventional RT-PCR, western blotting and immunofluorescence were used to detect the expression of GRP78 at the mRNA and protein levels in the NCI-H446 cell line treated with varying amounts of SILA409. The viability of cells treated with VP-16 was examined by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and apoptosis was studied via DAPI staining. The Ca2+ ionophore A23187 was used as an upregulator of GRP78. Results: The expression of GRP78 at the mRNA and protein levels in the A23187 Ca2+ ionophore-induced and SILA409-post-treated cells was significantly lower than that in the positive control in the A23187-treated group (p50 values for VP-16 in the SILA409-treated and A23187-pretreated and SILA409-post-treated groups were obviously decreased as compared with the A23187-treated group (33.16±4.91 vs 47.21±8.34, and 33.05±2.97 vs 47.21±8.34, respectively, p2+ ionophore followed by SILA409 treatment was significantly decreased as compared with that of the Ca 2+ ionophore-treated cells. The apoptosis induced by SILA409 treatment, in Ca2+ ionophore-pretreated and SILA409-post-treated cells was significantly increased relative to Ca2+ ionophore-treated cells. An elevated glucose concentration itself does not affect the MDR-reversing effect of SILA409. Conclusion: SILA409 can significantly decrease the overexpression of GRP78 induced by A23187 and increase the sensitivity to VP-16 in the NCI-H446 cell line.

AB - Aim: To investigate the effects of an MDR inhibitor and Ca2+ antagonist, the SILA409, on the expression of glucose-regulated protein 78 (GRP78) and the resistance to VP-16 in the NCI-H446 cell line. Methods: Conventional RT-PCR, western blotting and immunofluorescence were used to detect the expression of GRP78 at the mRNA and protein levels in the NCI-H446 cell line treated with varying amounts of SILA409. The viability of cells treated with VP-16 was examined by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and apoptosis was studied via DAPI staining. The Ca2+ ionophore A23187 was used as an upregulator of GRP78. Results: The expression of GRP78 at the mRNA and protein levels in the A23187 Ca2+ ionophore-induced and SILA409-post-treated cells was significantly lower than that in the positive control in the A23187-treated group (p50 values for VP-16 in the SILA409-treated and A23187-pretreated and SILA409-post-treated groups were obviously decreased as compared with the A23187-treated group (33.16±4.91 vs 47.21±8.34, and 33.05±2.97 vs 47.21±8.34, respectively, p2+ ionophore followed by SILA409 treatment was significantly decreased as compared with that of the Ca 2+ ionophore-treated cells. The apoptosis induced by SILA409 treatment, in Ca2+ ionophore-pretreated and SILA409-post-treated cells was significantly increased relative to Ca2+ ionophore-treated cells. An elevated glucose concentration itself does not affect the MDR-reversing effect of SILA409. Conclusion: SILA409 can significantly decrease the overexpression of GRP78 induced by A23187 and increase the sensitivity to VP-16 in the NCI-H446 cell line.

KW - Disiloxane

KW - GRP78

KW - Multidrug resistance

KW - SCLC

KW - SILA409

KW - VP-16

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