Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro

Abstract The application of chemotherapy in non‐small cell lung cancer (NSCLC) is limited by the toxicity to normal cells and the development of multi‐drug resistance. Targeted chemotherapy using cytotoxic analogs against specific receptors on cancer cells could be a less toxic and more efficacious...

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Autores principales:	Yanguo Liu, Handai Xia, Yawei Wang, Wenfei Han, Jing Qin, Wenjuan Gao, Xun Qu, Xiuwen Wang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cytotoxic analogs non‐small cell lung cancer paclitaxel resistance somatostatin receptors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9e9163898c474b04a946574518d93884
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spelling	oai:doaj.org-article:9e9163898c474b04a946574518d938842021-11-14T23:28:26ZTargeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro1759-77141759-770610.1111/1759-7714.14182https://doaj.org/article/9e9163898c474b04a946574518d938842021-11-01T00:00:00Zhttps://doi.org/10.1111/1759-7714.14182https://doaj.org/toc/1759-7706https://doaj.org/toc/1759-7714Abstract The application of chemotherapy in non‐small cell lung cancer (NSCLC) is limited by the toxicity to normal cells and the development of multi‐drug resistance. Targeted chemotherapy using cytotoxic analogs against specific receptors on cancer cells could be a less toxic and more efficacious approach. We identified that the expressions of somatostatin receptor (SSTR) 2 and 5 in tumor tissues from NSCLC patients were higher than those in the adjacent normal tissues by immunohistochemistry, and therefore, cytotoxic somatostatin analogues might be applied for SSTRs‐mediated targeted therapy against NSCLC. Two cytotoxic analogs, paclitaxel‐octreotide (PTX‐OCT) and 2paclitaxel‐octreotide (2PTX‐OCT), were synthesized by linking one or two molecules of paclitaxel to one molecule of somatostatin analog octreotide. PTX‐OCT and 2PTX‐OCT significantly inhibited the growth and induced apoptosis of SSTR2‐ and SSTR5‐positive A549 cells, compared with the control (p < 0.01), and had less inhibitory effect on SSTR2‐ and SSTR5‐negative H157 cells than paclitaxel (p < 0.01). Moreover, compared with paclitaxel, PTX‐OCT conjugates induced lower expression of MDR‐1 gene both in vitro and in vivo. Three A549 paclitaxel‐resistant cell lines were established through different approaches, and the paclitaxel‐resistant cell showed higher sensitivity to PTX‐OCT conjugates than to paclitaxel, which might be because of the differential MDR‐related gene expressions and cell‐cycle distribution in paclitaxel‐resistant A549 cells. Our results suggested that PTX‐OCT conjugates could be potentially used for SSTRs‐mediated targeted therapy for NSCLC, especially for those with paclitaxel resistance and induced less multidrug resistance.Yanguo LiuHandai XiaYawei WangWenfei HanJing QinWenjuan GaoXun QuXiuwen WangWileyarticlecytotoxic analogsnon‐small cell lung cancerpaclitaxel resistancesomatostatin receptorsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENThoracic Cancer, Vol 12, Iss 22, Pp 3053-3061 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cytotoxic analogs non‐small cell lung cancer paclitaxel resistance somatostatin receptors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cytotoxic analogs non‐small cell lung cancer paclitaxel resistance somatostatin receptors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yanguo Liu Handai Xia Yawei Wang Wenfei Han Jing Qin Wenjuan Gao Xun Qu Xiuwen Wang Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro
description	Abstract The application of chemotherapy in non‐small cell lung cancer (NSCLC) is limited by the toxicity to normal cells and the development of multi‐drug resistance. Targeted chemotherapy using cytotoxic analogs against specific receptors on cancer cells could be a less toxic and more efficacious approach. We identified that the expressions of somatostatin receptor (SSTR) 2 and 5 in tumor tissues from NSCLC patients were higher than those in the adjacent normal tissues by immunohistochemistry, and therefore, cytotoxic somatostatin analogues might be applied for SSTRs‐mediated targeted therapy against NSCLC. Two cytotoxic analogs, paclitaxel‐octreotide (PTX‐OCT) and 2paclitaxel‐octreotide (2PTX‐OCT), were synthesized by linking one or two molecules of paclitaxel to one molecule of somatostatin analog octreotide. PTX‐OCT and 2PTX‐OCT significantly inhibited the growth and induced apoptosis of SSTR2‐ and SSTR5‐positive A549 cells, compared with the control (p < 0.01), and had less inhibitory effect on SSTR2‐ and SSTR5‐negative H157 cells than paclitaxel (p < 0.01). Moreover, compared with paclitaxel, PTX‐OCT conjugates induced lower expression of MDR‐1 gene both in vitro and in vivo. Three A549 paclitaxel‐resistant cell lines were established through different approaches, and the paclitaxel‐resistant cell showed higher sensitivity to PTX‐OCT conjugates than to paclitaxel, which might be because of the differential MDR‐related gene expressions and cell‐cycle distribution in paclitaxel‐resistant A549 cells. Our results suggested that PTX‐OCT conjugates could be potentially used for SSTRs‐mediated targeted therapy for NSCLC, especially for those with paclitaxel resistance and induced less multidrug resistance.
format	article
author	Yanguo Liu Handai Xia Yawei Wang Wenfei Han Jing Qin Wenjuan Gao Xun Qu Xiuwen Wang
author_facet	Yanguo Liu Handai Xia Yawei Wang Wenfei Han Jing Qin Wenjuan Gao Xun Qu Xiuwen Wang
author_sort	Yanguo Liu
title	Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro
title_short	Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro
title_full	Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro
title_fullStr	Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro
title_full_unstemmed	Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro
title_sort	targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer a549 cells in vitro
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/9e9163898c474b04a946574518d93884
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Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro

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