Abstract
Blue lasers are becoming more widely used in the diagnosis and treatment of bladder cancer; however, their photobiomodulation effects on bladder cancer cells remains unclear. The purpose of the current study was to explore the photobiomodulation effect of blue laser irradiation on bladder cancer progression and the associated mechanisms. The human uroepithelial cell line SV-HUC-1 and human bladder cancer cell lines T24 and EJ were exposed to blue laser irradiation (450 nm) at various energy densities, and cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and the levels of the proteins associated with the MAPK pathway proteins were determined. A significant decrease in cell viability was observed in a density-dependent manner after blue laser irradiation at > 4 J/cm2 in both bladder cancer cell lines. However, the blue laser did not reduce cell viability in SV-HUC-1 cells until the energy density exceeded 16 J/cm2. Meanwhile, Ki67 levels, reflecting cell proliferation and senescence, were also significantly decreased after blue laser irradiation at 4 J/cm2 and 8 J/cm2 in the absence of cell cycle arrest. Moreover, blue laser irradiation at 4 J/cm2 and 8 J/cm2 caused a reduction in cell migration and invasion and also reduced the expression levels of MMP-2, MMP-9, Snail, N-cadherin, phospho-MEK and phospho-ERK, and elevated the expression levels of E-cadherin. Meanwhile ERK activator(tBHQ) significantly reversed the irradiation-induced suppression of proliferation, migration and invasion in T24 and EJ cell lines. The present study showed that blue laser irradiation inhibited bladder cancer proliferation in a density-dependent manner and inhibited bladder cancer progression by suppressing migration, invasion, and the EMT process in T24 and EJ cell lines. This inhibition was possibly mediated via suppression of the MAPK/MEK/ERK pathway. Thus, the use of a low-energy blue laser in the diagnosis and treatment of bladder cancer is possibly safe and may have an anti-tumor effect.
Highlights
Bladder cancer is the fourth leading cancer in males with an estimated 81,400 newly diagnosed cases in the USA in 2020 [1], and it remains the most common malignancy in the urinary system, with an expected 549,000 new cases and 200,000 deaths worldwide in 2018 [2, 3]
No significant changes in apoptosis rate (Supplementary Figure 1), cell cycle distribution, and CDK4 (Cyclin-dependent kinase 4) expression (Figures 2C, D) were observed in either cell line. These findings suggest that blue laser irradiation could inhibit bladder cancer cell proliferation in the absence of cell cycle arrest
Despite that blue laser is becoming more widely used in the detection and treatment of bladder cancer, its photobiomodulation effect on bladder cancer cells has remained unclear
Summary
Bladder cancer is the fourth leading cancer in males with an estimated 81,400 newly diagnosed cases in the USA in 2020 [1], and it remains the most common malignancy in the urinary system, with an expected 549,000 new cases and 200,000 deaths worldwide in 2018 [2, 3]. 75% of bladder cancer cases are classified as non-muscle-invasive tumors [4]. Blue Laser on Bladder Cancer resection of bladder tumors and adjuvant therapy have been extensively used for the treatment of non-muscle invasive tumors, over 50% of the patients will eventually experience recurrence or progression [5, 6]. Muscle invasive tumors account for 25% of bladder cancer cases; they require radical surgery or radiotherapy, which often leads to a significant decline in health-related quality of life and poor prognosis [7]. It is imperative to explore new methods for specific and sensitive diagnosis as well as effective treatment of bladder cancer. Accurate staging, and complete tumor resection, numerous adjuvant methods have recently been developed by using noval techniques, including narrow-band imaging, photodynamic diagnosis (PDD), confocal laser endomicroscopy (CLE), and optical coherence tomography [8]. The main principle of these methods is the use of low-energy laser light to obtain specific histopathological images [8]
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