Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma
<i>Background and Objectives</i>: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRP...
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MDPI AG
2022-09-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/58/9/1229 |
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| author | Farhana Yahya Marina Mohd Bakri Mohammad Zakir Hossain Syarifah Nur Syed Abdul Rahman Aied Mohammed Alabsi Anand Ramanathan |
| author_facet | Farhana Yahya Marina Mohd Bakri Mohammad Zakir Hossain Syarifah Nur Syed Abdul Rahman Aied Mohammed Alabsi Anand Ramanathan |
| author_sort | Farhana Yahya |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRPV4′s involvement in OSCC. Thus, in this study, we investigate the effect of administering a TRPV4 agonist on angiogenesis in OSCC. <i>Materials and Methods:</i> Thirty-six Sprague Dawley (SD) rats were used in this study. 4-nitroquinoline 1-oxide (4NQO) was used to induce OSCC. Cisplatin (an anticancer drug), and GSK1016790A (an agonist for TRPV4) was used in this study. Immunohistochemistry was employed to examine the TRPV4 expression. An RT<sup>2</sup> Profiler PCR Array was performed for gene expression analysis of TRPV4, vascular growth factors that correspond directly with angiogenesis, such as angiopoietin (Ang-1 and Ang-2), and tyrosine kinase (Tie-1 and Tie-2) receptors. Tumor vessel maturity was assessed by microvessel density and microvessel-pericyte-coverage index. <i>Results:</i> RT<sup>2</sup> profiler PCR array showed significant elevated levels of Ang-1 (2.1-fold change; <i>p</i> < 0.05) and Tie-2 (4.5-fold change; <i>p</i> < 0.05) in OSCC following the administration of a combination of GSK1016790A and cisplatin. Additionally, the combination treatment significantly reduced the microvessel density (<i>p</i> < 0.01) and significantly increased the percentage of microvessels covered with pericytes (<i>p</i> < 0.01) in OSCC. Furthermore, tumor size was significantly reduced (<i>p</i> < 0.05) in rats that received cisplatin alone. The combination treatment also greatly reduced the tumor size; however, the data were not statistically significant. <i>Conclusions:</i> The findings suggest that combining a TRPV4 agonist with cisplatin for treatment of OSCC promote vessels normalization via modulation of Ang-1/Tie-2 pathway. |
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| spelling | doaj.art-55d6ad70cc004f3eae70dbb77a22a22a2023-11-23T17:40:02ZengMDPI AGMedicina1010-660X1648-91442022-09-01589122910.3390/medicina58091229Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell CarcinomaFarhana Yahya0Marina Mohd Bakri1Mohammad Zakir Hossain2Syarifah Nur Syed Abdul Rahman3Aied Mohammed Alabsi4Anand Ramanathan5Department of Oral and Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Oral and Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Oral Physiology, School of Dentistry, Matsumoto Dental University, 1780 Gobara Hirooka, Shiojiri, Nagano 399-0781, JapanDepartment of Oral and Craniofacial Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Jenjarom 42610, MalaysiaDepartment of Oral and Maxillofacial Clinical Sciences, Universiti Malaya, Kuala Lumpur 50603, Malaysia<i>Background and Objectives</i>: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRPV4′s involvement in OSCC. Thus, in this study, we investigate the effect of administering a TRPV4 agonist on angiogenesis in OSCC. <i>Materials and Methods:</i> Thirty-six Sprague Dawley (SD) rats were used in this study. 4-nitroquinoline 1-oxide (4NQO) was used to induce OSCC. Cisplatin (an anticancer drug), and GSK1016790A (an agonist for TRPV4) was used in this study. Immunohistochemistry was employed to examine the TRPV4 expression. An RT<sup>2</sup> Profiler PCR Array was performed for gene expression analysis of TRPV4, vascular growth factors that correspond directly with angiogenesis, such as angiopoietin (Ang-1 and Ang-2), and tyrosine kinase (Tie-1 and Tie-2) receptors. Tumor vessel maturity was assessed by microvessel density and microvessel-pericyte-coverage index. <i>Results:</i> RT<sup>2</sup> profiler PCR array showed significant elevated levels of Ang-1 (2.1-fold change; <i>p</i> < 0.05) and Tie-2 (4.5-fold change; <i>p</i> < 0.05) in OSCC following the administration of a combination of GSK1016790A and cisplatin. Additionally, the combination treatment significantly reduced the microvessel density (<i>p</i> < 0.01) and significantly increased the percentage of microvessels covered with pericytes (<i>p</i> < 0.01) in OSCC. Furthermore, tumor size was significantly reduced (<i>p</i> < 0.05) in rats that received cisplatin alone. The combination treatment also greatly reduced the tumor size; however, the data were not statistically significant. <i>Conclusions:</i> The findings suggest that combining a TRPV4 agonist with cisplatin for treatment of OSCC promote vessels normalization via modulation of Ang-1/Tie-2 pathway.https://www.mdpi.com/1648-9144/58/9/1229oral squamous cell carcinoma (OSCC)transient receptor potential vanilloid 4 (TRPV4)4-nitroquinoline 1-oxide (4NQO)angiogenesisvascular normalization |
| spellingShingle | Farhana Yahya Marina Mohd Bakri Mohammad Zakir Hossain Syarifah Nur Syed Abdul Rahman Aied Mohammed Alabsi Anand Ramanathan Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma Medicina oral squamous cell carcinoma (OSCC) transient receptor potential vanilloid 4 (TRPV4) 4-nitroquinoline 1-oxide (4NQO) angiogenesis vascular normalization |
| title | Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma |
| title_full | Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma |
| title_fullStr | Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma |
| title_full_unstemmed | Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma |
| title_short | Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma |
| title_sort | combination treatment of trpv4 agonist with cisplatin promotes vessel normalization in an animal model of oral squamous cell carcinoma |
| topic | oral squamous cell carcinoma (OSCC) transient receptor potential vanilloid 4 (TRPV4) 4-nitroquinoline 1-oxide (4NQO) angiogenesis vascular normalization |
| url | https://www.mdpi.com/1648-9144/58/9/1229 |
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