Blockade of Chloride Ion Transport Enhances the Cytocidal Effect of Hypotonic Solution in Gastric Cancer Cells

Iitaka, Daisuke; Shiozaki, Atsushi; Ichikawa, Daisuke; Kosuga, Toshiyuki; Komatsu, Shuhei; Okamoto, Kazuma; Fujiwara, Hitoshi; Ishii, Hiromichi; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

doi:10.1016/j.jss.2011.10.039

Cited by 28 publications

(37 citation statements)

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“…Therefore, we hypothesized that dialysate lavage induces cytotoxicity in certain gastric cancer cells with limited injury in the peritoneal mesothelium. MKN45 is a cell line established from poorly differentiated human gastric cancer, and it is more resistant to hypotonic lavage (e.g., distilled water) stress [7]. As shown in our in vitro study, MKN45 cells (and AGS, another poorly differentiated cell line) incubated with 1.5% dialysate fluid had more cell death than with NS.…”

Section: Discussionmentioning

confidence: 63%

“…Therefore, extensive lavage using a large amount of saline [5] or water [6] has been performed during the immediate postoperative period to mitigate tumor seeding. Some of the reported results are favorable [5,6], but some cancer cells (e.g., MKN45 cells) appear to be more resistant to hypotonic stress than others [7,8]. Therefore, the use of an alternative solution for intraperitoneal lavage should be further studied.…”

Section: Introductionmentioning

confidence: 99%

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Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal Implantation of Poorly Differentiated Gastric Cancer Cells

et al. 2015

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Background: Peritoneal lavage after cancer surgery is performed to reduce microscopic residual tumors in the peritoneum. This study evaluated the effects and mechanism of dialysate lavage in reducing the peritoneal implantation of gastric cancer cells. Methods: Gastric cancer cells (MKN45 or AGS) were cultured with 1.5% peritoneal dialysate (PD) or normal saline (NS) for 30 min. The in vitro cell susceptibility to dialysate, including cell proliferation, cell death, cleaved PARP expression, and mitochondrial membrane potential, was evaluated. A murine model for gastric cancer cell peritoneal seeding was established to test the effects of PD and NS lavage on animal survival and tumor growth. Results: A significant decrease in cell proliferation in PD and NS (75.2 ± 0.1 vs. 12.4 ± 0.2% in MKN45, p = 0.009; 58.2 ± 0.01 vs. 28.0 ± 0.01% in AGS, p = 0.008), an increase in mitochondrial permeability transition (93.0 ± 2.6 vs. 18.0 ± 2.9% in MKN45, p = 0.021; 86.8 ± 4.6 vs. 47.7 ± 10.2% in AGS, p < 0.001), and an increase in the expression of cleaved PARP and increased death (25.6 ± 9.4 vs. 16.9 ± 5.3% in MKN45, p = 0.031; 39.5 ± 5.1 vs. 20.9 ± 3.9% in AGS, p = 0.008) were recorded for gastric cancer cells separately exposed to PD and NS. Twenty-four days after inoculating MKN45 cells (5 × 10⁶/0.1 ml) in the peritoneal cavity, the average number of seeded tumors was 67.3 ± 10.8, 92.3 ± 6.0, and 29.2 ± 16.7 (p = 0.032), and the total weight of tumors was 0.98 ± 0.21, 0.58 ± 0.12, and 0.31 ± 0.17 g (p = 0.008), respectively, for mice receiving sham operation, NS lavage, and PD lavage. The 45-day survival rate for the PD lavage group was 22% compared to 0% for the sham injection and NS lavage groups (p = 0.034). Conclusion: PD induced significant cytotoxicity in gastric cancer cells that was related to mitochondrial perturbation. The use of PD lavage was effective in reducing the peritoneal implantation of gastric cancers in a murine model.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal Implantation of Poorly Differentiated Gastric Cancer Cells

et al. 2015

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“…In this light, and in light of the data presented in this work, it makes sense to include treatments that target osmotic conditions in therapies against certain carcinoma types (Balachandran et al, 2015;Grohé and Berardi, 2015). Furthermore, lavages with distilled water during cancer surgery (Iitaka et al, 2012), or hypotonic approaches to improve the uptake of chemotherapeutics by tumor cells (Stephen et al, 1990), should be used with caution.…”

Section: The Cooperation Between Atp1b1a and Lgl2mentioning

confidence: 99%

509 Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

Hatzold

Beleggia

Herzig

et al. 2016

Journal of Investigative Dermatology

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The molecular pathways underlying tumor suppression are incompletely understood.Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFkB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression.

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“…The regulation of extracellular osmolality is a promising method, with previous studies demonstrating the cytocidal effects of hypotonic treatments on cancer cells [10–12]. We recently examined changes in the cellular morphology and volume of gastric cancer cells subjected to hypotonic shock using several unique methods and apparatus, such as a differential interference contrast microscope connected to a high-speed digital video camera and a high-resolution flow cytometer [13]. Our findings confirmed the cytocidal effects of hypotonic shock on gastric cancer cells in vitro [13].…”

Section: Introductionmentioning

confidence: 99%

“…We recently examined changes in the cellular morphology and volume of gastric cancer cells subjected to hypotonic shock using several unique methods and apparatus, such as a differential interference contrast microscope connected to a high-speed digital video camera and a high-resolution flow cytometer [13]. Our findings confirmed the cytocidal effects of hypotonic shock on gastric cancer cells in vitro [13]. However, the effects of hypotonic treatments on the development of peritoneal dissemination from gastric cancer and their safeness in vivo have not yet been fully evaluated.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a Hypotonic Treatment for Peritoneal Dissemination from Gastric Cancer Cells: AnIn VivoEvaluation

Shiozaki

Ichikawa

Takemoto

et al. 2014

BioMed Research International

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The aim of the present study was to determine the efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells using an in vivo model. We firstly evaluated the toxicity of a peritoneal injection of distilled water (DW) (2 mL for 3 days) in mice. Macroscopic and microscopic examinations revealed that the peritoneal injection of DW did not severely damage the abdominal organs of these mice. MKN45 gastric cancer cells preincubated with NaCl buffer or DW for 20 minutes in vitro were then intraperitoneally injected into nude mice, and the development of dissemination nodules was analyzed. The total number, weight, and volume of the dissemination nodules were significantly decreased by the DW preincubation. We then determined whether the peritoneal injection of DW inhibited the establishment of peritoneal dissemination. After a peritoneal injection of MKN45 cells into nude mice, NaCl buffer or DW was injected into the abdominal cavity for 3 days. The total volume of dissemination nodules was significantly lower in DW-injected mice than in NaCl-injected mice. In conclusion, we demonstrated the safeness of a peritoneal injection of DW. Furthermore, the development of dissemination nodules from gastric cancer cells was prevented by a preincubation with or peritoneal injection of DW.

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Blockade of Chloride Ion Transport Enhances the Cytocidal Effect of Hypotonic Solution in Gastric Cancer Cells

Cited by 28 publications

References 28 publications

Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal Implantation of Poorly Differentiated Gastric Cancer Cells

Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal Implantation of Poorly Differentiated Gastric Cancer Cells

509 Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

Efficacy of a Hypotonic Treatment for Peritoneal Dissemination from Gastric Cancer Cells: AnIn VivoEvaluation

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