prvič objavljeno v spletišču 10. marca 2009
Raziskavo opravili:
Izvleček
Zaradi povečane presnove glukoze in slabe prekrvavitve je zunanji pH trdih tumorjev kisel. Ugotovljeno je, da kisel pH spodbuja vdiranje tumorskih celic in njihov raztos in vitro in v celicah že pred injekcijskim vbrizganjem v repno veno in vivo. S to raziskavo se želi ugotoviti, ali se z zmanjšanjem kislosti tumorja zmanjša tudi raztros rakavih celic in vivo.
Raziskava je pokazala, da NaHCO3 zviša pH tumorja in zmanjša samodejno širjenje raka pri poskusnih miškah z rakom dojke. Opisano zdravljenje je občutno, za 31 %, zvišalo izvencelični pH, ne pa tudi znotrajceličnega, merjeno po magnetno-rezonačni spektroskopski lestvici in z merjenjem kisline, ki jo je rastoči tumor izločal v opazovanem gojišču, s fluorescentno mikroskopijo. Zdravljenje z NaHCO3 je tudi zmanjšalo stopnjo prizadetosti bezgavk, ni pa vplivalo na kroženje tumorskih celic v obtočilih, kar navaja na sklep, da zmanjšanje raztosa rakavih celic v organe ni bilo posledica povečanega vdora tujkov v obtočila.
Prav nasprotno, NaHCO3 je občutno zmanjšala širjenje raka v jetra po njenem injiciranju v vranico, kar navaja na sklep, da je zavrla vdiranje tujkov v obtočila in njihovo širjenje po telesu. Pri drugih vrst raka, z injekcijo vbrizganih v rep proučevanih miši, se je soda različno obnesla: zavrla je raztros prostatnih rakavih celic PC3M, ne pa melanomskih B16.
Čeprav ni z gotovostjo ugotovljeno, kako deluje zdravljenje s sodo bikarbono, je ugotovljeno, da nizek pH zvišuje izločanje aktivnega B-katepsina, ki je pomemben dejavnik pri spreminjanju proteaznih encimov.
vir: Cancer research, 2009, 6. št. (69), 2260.–8. str. | PMID 19276390 [izdaja se pripravlja]
Original text:
Abstract
The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will reduce the incidence of in vivo metastases.
They show that oral NaHCO3 selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer. This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors by 31P magnetic resonance spectroscopy and the export of acid from growing tumors by fluorescence microscopy of tumors grown in window chambers.
NaHCO3 therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation.
In contrast, NaHCO3 therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization. In tail vein injections of alternative cancer models, bicarbonate had mixed results, inhibiting the formation of metastases from PC3M prostate cancer cells, but not those of B16 melanoma. Although the mechanism of this therapy is not known with certainty, low pH was shown to increase the release of active cathepsin B, an important matrix remodeling protease.
Source: Cancer Res 2009;69(6):2260–8 | PMID: 19276390 [PubMed - in process]
