Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82 human bladder cancer cells

Abstract

Abstract. The occurrence of resistance to mitomycin C (MMC) often limits its clinical effectiveness. Combination therapy thus is employed to overcome this treatment resistance. The present study aimed to establish a novel J82 bladder cancer cell line so as to study the effect of inhibition of aquaporin 1 (AQP-1) on chemotherapy sensitivity of J82 bladder cancer cells. A novel J82 bladder cancer cell line whose expression of AQP-1 is inhibited was established through transfection of J82 cells with newly constructed recombinant plasmid. The resulting cell line was designated J82-short hairpin (sh)AQP1 and was subjected to further analyses together with J82 cell line. Reverse transcription-polymerase chain reaction was used to quantify the expression of AQP-1mRNA in the cells; cell viability was analyzed with MTT assay and apoptosis was measured by flow cytometry. The expression of cell proliferation and cell apoptosis-associated proteins, proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3, were detected by Western blot. A statistically significant decrease in the transcription and expression of AQP1 was observed in the J82-shAQP1 cells as compared with J82 cells. J82-shAQP1 cells treated by MMC, also had a lower cell viability than J82 cells treated by MMC and showed enhanced apoptosis. Western blot analysis revealed J82-shAQP1 cells treated by MMC had less expression of PCNA, lower bcl-2/Bax ratio and more expression of caspase-3 as compared with the J82 cells treated by MMC. Selective inhibition of AQP-1 enhanced MMC chemotherapy sensitivity of J82 bladder cancer cells, suggesting combination of AQP-1 inhibition with MMC treatment as a promising treatment strategy to overcome bladder cancer treatment resistance.

Aquaporins: New players in breast cancer progression and treatment response

“…Investigating the mechanism regulating chemosensitivity uncovered that cytoplasmic AQP1 and glycogen synthase kinase-3b (GSK3b) interact via 12 armadillo repeats of bcatenin, leading to b-catenin accumulation and its interaction with Topo IIa and enhancing its activity, which increased the sensitivity to anthracycline treatment (91). This association with chemotherapy sensitivity via AQP1 occurred not only in breast cancer but also in human bladder cancer cells, where AQP1 inhibition enhanced mitomycin C sensitivity, and also in colorectal and ovarian cancers (130)(131)(132).…”

Hydropenia may accelerates the progression of orthotopic bladder cancer induced by N-methyl-N-nitrosourea by increasing the expression levels of AQP1, AQP3, and AQP4

“…Their findings demonstrated the potential significance of AQP1 to guide bladder carcinoma diagnosis and treatment. Furthermore, Zhang et al (15) reported that selective inhibition of AQP1 enhanced the sensitivity of J82 BCa cells to mitomycin C. Moreover, AQP3, AQP4, AQP7, AQP9, and AQP11 transcripts were detected in both freshly isolated urothelial cells and cultured urothelial cells. At the protein level, an unequivocal expression of AQP3 was also observed, with immunohistochemistry revealing intense staining of cell membranes in both the basal and intermediate layers of normal bladder urothelial tissue (10).…”

A Novel Scoring System for Risk Assessment of Elderly Patients With Cytogenetically Normal Acute Myeloid Leukemia Based on Expression of Three AQP1 DNA Methylation-Associated Genes

“…It's worth noting that most studies show that AQP1 gene acts as an oncogene in various solid cancers to promote cancer development (12)(13)(14), whereas only a few studies report AQP1 as a tumor suppressor that inhibits tumor growth (21,58). Recently, Marietta Tan et al also showed that AQP1 was epigenetically downregulated by promoter methylation and was associated with improved prognosis in salivary gland adenoid cystic carcinoma (20).…”

“…facilitates transcellular water transportation (11). AQP1 plays an oncogenic role in many types of solid cancer, including colorectal cancer, breast cancer, bladder cancer (12)(13)(14). Functionally, AQP1 regulates cell proliferation, invasion, metastasis and angiogenesis.…”