EFFECT OF DICHLOROACETATE ON LEWIS LUNG CARCINOMA GROWTH AND METASTASIS

A hallmark of malignancy is excessive tumor glycolysis, even in the presence of oxygen, which causes lactacidosis in the tumor microenvironment and favors tumor cell proliferation and survival. For this reason antimetabolic agents which target tumor cell metabolism are being researched extensively as promising anticancer drugs. Aim: To study the effect of lactacidosis on survival of Lewis lung carcinoma (LLC) cells at the conditions of nutritional substrate deficiency in vitro and evaluate antitumor and antimetastatic activity against LLC/ R9 in vivo. Materials and Methods: LLC variant LLC/R9 was used as experimental tumor model. Tumor cell viability was determined using trypan blue staining. Apoptosis level was counted with the use of Hoechst 33258 dye. Lactate content in the tumor tissue was evaluated by enzyme method with the use of lactate dehydrogenase. Reactive oxygen species was determined using 2.7-dichlorofluorescein diacetate. Effects of dichloroacetate (DCA) on the growth and metastasis of LLC/R9 were analyzed by routine procedures. Evaluation of DCA effect toward electron-transport chain (ETC) components was performed using EPR. Results: It has been shown that at the conditions of lactacidosis and glucose deficiency, LLC/R9 cell viability in vitro was higher by 30% (р < 0.05) and apoptosis level was triply lower (р < 0.05) than these indices at the conditions of glucose deficiency only. In mice with transplanted LLC/R9 tumors treated for 3 weeks per os with DCA at the total dose of 1.5 g/kg of body weight starting from the next day after tumor transplantation, the primary tumor volume was just by 30% lower than that in control group. At the same time, the number and volume of lung metastases in animals treated with DCA were by 59% (р < 0.05) and 94% (р < 0.05) lower, respectively, than these indices in the control group. DCA treatment resulted in nearly 30% increase (р < 0.05) of lactate content in tumor tissue compared to that in the control, but did not affect significantly the levels of heme iron complexes with NO (at gmed = 2.007) in mitochondrial ETC proteins and Fe-S cluster proteins (at g = 1.94) in tumor cells. Conclusions: It has been shown that lactacidosis significantly promoted LLC/R9 cell survival at the conditions of glucose deficiency in vitro. If LLC/R9 developed in vivo, DCA as the compound with antilactacidosis activity did not suppress significantly the primary tumor growth but exerted significant antimetastatic activity.

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In Vitro and in Vivo Selection of two Lewis Lung Carcinoma Cell Lines

Tumori Journal ◽

10.1177/030089167906500601 ◽

1979 ◽

Vol 65 (6) ◽

pp. 657-664 ◽

Cited By ~ 15

Author(s):

Ada Sacchi ◽

Anna Corsi ◽

Marco Caputo ◽

Gabriella Zupi

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Lung Metastases ◽

Tumor Cell Lines ◽

Lewis Lung ◽

Selection Of

Two tumor cell lines adapted to grow in vitro were originated from an explant of lung metastases of Lewis lung carcinoma. These lines differ in their malignancy when reinoculated into syngeneic animals; nevertheless, they do not show any difference for their in vitro clonogenic ability. From these lines 2 in vivo sublines of 3LL carcinoma were developed. The TD 50 of the 2 in vivo sublines are different, and both the values obtained are lower than that of the original line. These results are interpreted as a selection of more malignant tumor cell lines.

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Effects of Sevoflurane on Lewis Lung Carcinoma Cell Proliferation In Vivo and In Vitro

Medicina ◽

10.3390/medicina57010045 ◽

2021 ◽

Vol 57 (1) ◽

pp. 45

Author(s):

Yeojung Kim ◽

Sangwon Yun ◽

Keun-A Shin ◽

Woosuk Chung ◽

Youngkwon Ko ◽

...

Keyword(s):

Cell Proliferation ◽

Lung Carcinoma ◽

Tumor Size ◽

Lewis Lung Carcinoma ◽

In Vitro Study ◽

Control Group ◽

Lewis Lung ◽

And Control

Background and objectives: There are several studies that sevoflurane could enhance proliferation of cancer cells, while others suggest no effect on clinical outcome. We conducted in vivo and in vitro experiments to investigate the effects of sevoflurane, a volatile anesthetic, on proliferation and outcomes of Lewis lung carcinoma (LLC) cells. Materials and Methods: A total of 37 mice were injected with LLC cells to compare the tumor size and survival of the sevoflurane exposed group (sevo group) and control group. The sevo group was exposed to 2% sevoflurane and 4 L/min of oxygen for 1 h per day 3 times per week, and the control group was exposed only to 4 L/min of oxygen. In vitro study, 12 plates incubated with LCC cells. 6 plates were exposed to 2% sevoflurane for 1 hr/day for 3 days and 6 plates were not exposed, and cell proliferation was compared after 3 days. Results: There were no significant differences in survival or tumor size between mice exposed to sevoflurane and control mice (survival: 29.06 ± 4.45 vs. 28.76 ± 3.75, p = 0.836; tumor size: 0.75 (0.41–1.02) vs. 0.49 (0.11–0.79), p = 0.153). However, in vitro study, the proliferation of LLC cells exposed to sevoflurane increased by 9.2% compared to the control group (p = 0.018). Conclusions: Sevoflurane (2 vol%) exposure could promote proliferation of LLC cells in vitro environment, but may not affect proliferation of LLC cells in vivo environment. These results suggest that in vitro studies on the effects of anesthetics on cancer may differ from those of in vivo or clinical studies.

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Asian ginseng extract inhibits in vitro and in vivo growth of mouse lewis lung carcinoma via modulation of ERK-p53 and NF-κB signaling

Journal of Cellular Biochemistry ◽

10.1002/jcb.22778 ◽

2010 ◽

Vol 111 (4) ◽

pp. 899-910 ◽

Cited By ~ 38

Author(s):

Vincent Kam Wai Wong ◽

Simon Shiu Fai Cheung ◽

Ting Li ◽

Zhi-Hong Jiang ◽

Jing-Rong Wang ◽

...

Keyword(s):

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Lewis Lung ◽

Ginseng Extract ◽

In Vivo Growth

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Relationship of cell cycle parameters to in vitro and in vivo chemosensitivity for a series of Lewis lung carcinoma lines

European Journal of Cancer ◽

10.1016/0959-8049(92)90537-c ◽

1992 ◽

Vol 28 (8-9) ◽

pp. 1427-1431 ◽

Cited By ~ 13

Author(s):

Karen M. Holdaway ◽

Graeme J. Finlay ◽

Bruce C. Baguley

Keyword(s):

Cell Cycle ◽

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Lewis Lung ◽

Relationship Of

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Effect of Micelle-Incorporated Cisplatin With Sizes Ranging From 8 to 40 nm for the Therapy of Lewis Lung Carcinoma

Frontiers in Pharmacology ◽

10.3389/fphar.2021.632877 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhicheng Wang ◽

Yumin Li ◽

Tong Zhang ◽

Hongxia Li ◽

Zhao Yang ◽

...

Keyword(s):

Block Copolymers ◽

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Drug Loading ◽

Complexation Reaction ◽

Lewis Lung ◽

Antitumor Effects ◽

Lung Carcinoma Cells

Insufficient transport of therapeutic cargo into tumor bed is a bottleneck in cancer nanomedicine. Block copolymers are promising carriers with smaller particle size by ratio modification. Here, we constructed cisplatin nanoparticles with sizes ranging from 8 to 40 nm to study the permeability and therapy of Lewis lung carcinoma. We synthesized methoxypoly(ethylene glycol)2000-block poly(L-glutamic acid sodium salt)1979 loading cisplatin through complexation reaction. The cisplatin nanomedicine has high drug loading and encapsulation efficiency. In vitro data demonstrated that cisplatin nanoparticles had equivalent growth-inhibiting effects on Lewis lung carcinoma cells compared to free cisplatin. In vivo evidences showed cisplatin nanoparticles had superior antitumor effects on the Lewis lung carcinoma mouse model with no obvious side effects. All results indicated that optimizing the ratio of block copolymers to obtain smaller sized nanomedicine could act as a promising strategy for overcoming the inadequate accumulation in poorly vascularized tumors.

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